Endocrine - Pancreas Development: Difference between revisions
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==Introduction== | ==Introduction== | ||
[[File:Human- pancreatic adult islet.jpg|thumb|350px|Human Pancreatic Islets (Islets of Langerhans) | [[File:Human- pancreatic adult islet.jpg|thumb|350px|Human Pancreatic Islets (Islets of Langerhans){{#pmid:18958289|PMID18958289}}]] | ||
The pancreas is a two-headed organ, not only in origin but also in function. In origin, the pancreas develops from two separate primordia. In function, the organ has both endocrine function in relation to regulating blood glucose (and also other hormone secretions) and gastrointestinal function as an exocrine (digestive) organ, see | The pancreas is a two-headed organ, not only in origin but also in function. In origin, the pancreas develops from two separate primordia. In function, the organ has both endocrine function in relation to regulating blood glucose (and also other hormone secretions) and gastrointestinal function as an exocrine (digestive) organ, see {{exocrine pancreas}}. | ||
In recent years there has been much research due to the [[#Diabetes|increasing incidence of diabetes]] in humans and the potential for stem cell therapeutics. Much is now known about the epithelial/mesenchymal and molecular regulation of pancres development. | In recent years there has been much research due to the [[#Diabetes|increasing incidence of diabetes]] in humans and the potential for stem cell therapeutics. Much is now known about the epithelial/mesenchymal and molecular regulation of pancres development. | ||
At the foregut/midgut junction the septum transversum generates 2 pancreatic buds (dorsal and ventral endoderm) which will fuse to form the pancreas. The dorsal bud arises first and generates most of the pancreas. The ventral bud arises beside the bile duct and forms only part of the head and uncinate process of the pancreas. | At the foregut/midgut junction the septum transversum generates 2 pancreatic buds (dorsal and ventral endoderm) which will fuse to form the pancreas. The dorsal bud arises first and generates most of the pancreas. The ventral bud arises beside the bile duct and forms only part of the head and uncinate process of the pancreas. | ||
In the fetal period islet cell clusters (icc) differentiate from | |||
In the fetal period islet cell clusters (icc) differentiate from pancreatic bud {{endoderm}}. These cell clusters form acini and ducts (exocrine). On the edge of these cell clusters pancreatic islets (endocrine) also form. Pancreatic hormonal function is mainly to secrete insulin and glucagon that together regulate blood glucose levels. Pancreatic progenitor cells give rise to five endocrine cell types secreting: insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. Furthermore gastrin, secreted by {{stomach}} G-cells, is also embryonically expressed in the pancreas but disappears after birth.{{#pmid:23940571|PMID23940571}} | |||
The pancreas exocrine function begins after birth, while the endocrine function (hormone release) can be measured from 10 to 15 weeks onward. At this stage, it is not clear what the exact roles of these hormones are in regulating fetal growth. | The pancreas exocrine function begins after birth, while the endocrine function (hormone release) can be measured from 10 to 15 weeks onward. At this stage, it is not clear what the exact roles of these hormones are in regulating fetal growth. | ||
[[File:Pancreas adult.jpg|thumb|Pancreas adult]] | [[File:Pancreas adult.jpg|thumb|Pancreas adult]] | ||
* Functions - exocrine (amylase, alpha-fetoprotein), 99% by volume; endocrine (pancreatic islets) 1% by volume | * Functions - exocrine (amylase, alpha-fetoprotein), 99% by volume; endocrine (pancreatic islets) 1% by volume about 1 million islets | ||
* Exocrine function - begins after birth | * Exocrine function - begins after birth | ||
* Endocrine function - from 10 to 15 weeks onward hormone release | * Endocrine function - from 10 to 15 weeks onward hormone release | ||
** exact roles of hormones in regulating fetal growth? | ** exact roles of hormones in regulating fetal growth? | ||
:'''Links:''' [[Endocrine - Pancreas Development|Endocrine Pancreas]] | [[Gastrointestinal_Tract_-_Pancreas_Development|Exocrine Pancreas]] | |||
{{Endocrine Links}} | |||
See also: [[Lecture - Gastrointestinal Development]] | [[Abnormal Development - Maternal Diabetes|Maternal Diabetes]] | |||
::[[Embryology_History|Historic Embryology]]: [[Book - Manual of Human Embryology 17-8|1912 Pancreas Development]] | [[Paper - Some Observations on the Development of the Ventral Pancreas in Man|1930 Ventral Pancreas]] | |||
== Some Recent Findings == | == Some Recent Findings == | ||
[[File:Molecular_endocrine_pancreas_cells_01.jpg|thumb|300px|alt=Molecular Development of Endocrine Pancreas Cells|Molecular Development of Endocrine Pancreas Cells{{#pmid:23940571|PMID23940571}}[[#Molecular|Molecular Pancreas]]]] | |||
{| | {| | ||
|-bgcolor="F5FAFF" | |-bgcolor="F5FAFF" | ||
| | | | ||
* ''' | * '''Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation'''{{#pmid:30379923|PMID30379923}} "Various subtypes of enteroendocrine cells (EECs) are present in the gut epithelium. EECs and pancreatic β-cells share similar pathways of differentiation during embryonic development and after birth. In this study, similarities between EECs and β-cells were evaluated in detail. To obtain specific subtypes of EECs, cell sorting by flow cytometry was conducted from STC-1 cells (a heterogenous EEC line), and each single cell was cultured and passaged. Five EEC subtypes were established according to hormone expression, measured by quantitative RT-PCR and immunostaining: L, K, I, G and S cells expressing glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, cholecystokinin, gastrin and secretin, respectively. Each EEC subtype was found to express not only the corresponding gut hormone but also other gut hormones....Genes for insulin secretion-related proteins were mostly enriched in EECs. However, gene expression of transcription factors crucial in mature β-cells, such as PDX1, MAFA and NKX6.1, were remarkably low in all EEC subtypes. Each EEC subtype showed variable methylation in three cytosine-guanosine dinucleotide sites in the insulin gene (Ins2) promoter, which were fully unmethylated in MIN6 cells. In conclusion, our data confirm that five EEC subtypes are closely related to β-cells, suggesting a potential target for cell-based therapy in type 1 diabetes." | ||
* '''Relative roles of the different Pax6 domains for pancreatic alpha cell development.''' | |||
* '''Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis'''{{#pmid:30135482|PMID30135482}} "Decoding the molecular composition of individual Ngn3 + endocrine progenitors (EPs) during pancreatic morphogenesis could provide insight into the mechanisms regulating hormonal cell fate. Here, we identify population markers and extensive cellular diversity including four EP subtypes reflecting EP maturation using high-resolution single-cell RNA-sequencing of the e{{ME14.5}} and e{{ME16.5}} {{mouse}} pancreas. While e{{ME14.5}} and e{{ME16.5}} EPs are constantly born and share select genes, these EPs are overall transcriptionally distinct concomitant with changes in the underlying epithelium. As a consequence, e16.5 EPs are not the same as e{{ME14.5}} EPs: e{{ME16.5}} EPs have a higher propensity to form beta cells. Analysis of e{{ME14.5}} and e{{ME16.5}} EP chromatin states reveals temporal shifts, with enrichment of beta cell motifs in accessible regions at later stages. Finally, we provide transcriptional maps outlining the route progenitors take as they make cell fate decisions, which can be applied to advance the in vitro generation of beta cells." | |||
* '''Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity'''{{#pmid:30092080|PMID30092080}} "In the context of type 1 diabetes research and the development of insulin-producing β-cell replacement strategies, whether pancreatic ductal cells retain their developmental capability to adopt an endocrine cell identity remains debated, most likely due to the diversity of models employed to induce pancreatic regeneration. In this work, rather than injuring the pancreas, we developed a mouse model allowing the inducible misexpression of the proendocrine gene Neurog3 in ductal cells in vivo. These animals developed a progressive islet hypertrophy attributed to a proportional increase in all endocrine cell populations. Lineage tracing experiments indicated a continuous neo-generation of endocrine cells exhibiting a ductal ontogeny. Interestingly, the resulting supplementary β-like cells were found to be functional. Based on these findings, we suggest that ductal cells could represent a renewable source of new β-like cells and that strategies aiming at controlling the expression of Neurog3, or of its molecular targets/co-factors, may pave new avenues for the improved treatments of diabetes." | |||
|} | |||
{| class="wikitable mw-collapsible mw-collapsed" | |||
! More recent papers | |||
|- | |||
| [[File:Mark_Hill.jpg|90px|left]] {{Most_Recent_Refs}} | |||
Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pancreas+Embryology ''Pancreas Embryology''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pancreas+Development ''Pancreas Development''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Endocrine+Pancreas+Development ''Endocrine Pancreas Development''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=Exocrine+Pancreas+Development ''Exocrine Pancreas Development''] | [http://www.ncbi.nlm.nih.gov/pubmed/?term=pancreatic+islet ''pancreatic islet''] | |||
|} | |||
{| class="wikitable mw-collapsible mw-collapsed" | |||
! Older papers | |||
|- | |||
| {{Older papers}} | |||
* '''Gastrin: a distinct fate of neurogenin3 positive progenitor cells in the embryonic pancreas'''{{#pmid:23940571|PMID23940571}} "Neurogenin3(+) (Ngn3(+)) progenitor cells in the developing pancreas give rise to five endocrine cell types secreting insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. Gastrin is a hormone produced primarily by G-cells in the stomach, where it functions to stimulate acid secretion by gastric parietal cells. Gastrin is expressed in the embryonic pancreas and is common in islet cell tumors, but the lineage and regulators of pancreatic gastrin(+) cells are not known. We report that gastrin is abundantly expressed in the embryonic pancreas and disappears soon after birth." | |||
* '''Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation'''{{#pmid:22084084|PMID22084084}} "Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis." | |||
* '''Pancreatic mesenchyme regulates epithelial organogenesis throughout development'''{{#pmid:21909240|PMID21909240}} "The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. ...Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively." | |||
* '''Relative roles of the different Pax6 domains for pancreatic alpha cell development.'''{{#pmid:20377917|PMID20377917}} "The transcription factor Pax6 functions in the specification and maintenance of the differentiated cell lineages in the endocrine pancreas. It has two DNA binding domains, the paired domain and the homeodomain, in addition to a C-terminal transactivation domain. The phenotype of Pax6-/- knockout mice suggests non-redundant functions of the transcription factor in the development of glucagon-expressing alpha-cells as this cell type is absent in the mutants." | |||
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* Duodenum growth/rotation - brings ventral and dorsal buds together, fusion of buds | * Duodenum growth/rotation - brings ventral and dorsal buds together, fusion of buds | ||
* Pancreatic duct - ventral bud duct and distal part of dorsal bud, exocrine function | * Pancreatic duct - ventral bud duct and distal part of dorsal bud, exocrine function | ||
* Islet cells - cords of endodermal cells form ducts, from which cells bud off to form islets | * Islet cells - cords of endodermal cells form ducts, from which cells bud off to form islets{{#pmid:18508724|PMID18508724}} | ||
==Human Pancreas Timeline== | ==Human Pancreas Timeline== | ||
[[File:Bailey274.jpg| | {{Human Pancreas Timeline table1}} | ||
[[File: | <br> | ||
{| | |||
| [[File:Bailey274.jpg|350px]] | |||
| [[File:Stage22_pancreas.jpg|350px]] | |||
|- | |||
|Human (week 4) pancreatic buds | |||
| Human (week 8, Stage 22) pancreas | |||
|} | |||
<br> | |||
* Week 7 to 20 - pancreatic hormones secretion increases, small amount maternal insulin | * Week 7 to 20 - pancreatic hormones secretion increases, small amount maternal insulin | ||
* Week 10 - glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins | * Week 10 - glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins | ||
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[[File:Human_fetal_pancreas_anatomy_cartoon.jpg|500px]] | [[File:Human_fetal_pancreas_anatomy_cartoon.jpg|500px]] | ||
Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries. | Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries.{{#pmid:20376893|PMID20376893}} | ||
A diagram showing joining processes between the dorsal and ventral primordia of the pancreas as well as the hypothetical rotation of the duodenum along a left-right axis. Viewed from the posterosuperior side of the body. A horizontal plane including most parts of the duodenum is shown to emphasize, in contrast to adults, the course of the second portion (D2) directing posteriorly rather than inferiorly. | A diagram showing joining processes between the dorsal and ventral primordia of the pancreas as well as the hypothetical rotation of the duodenum along a left-right axis. Viewed from the posterosuperior side of the body. A horizontal plane including most parts of the duodenum is shown to emphasize, in contrast to adults, the course of the second portion (D2) directing posteriorly rather than inferiorly. | ||
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==Developing Pancreatic Islets== | ==Developing Pancreatic Islets== | ||
{| | {| | ||
| '''Model of endocrine cell and vessel organization in human islets''' | | '''Model of endocrine cell and vessel organization in human islets'''{{#pmid:20185817|PMID20185817}} | ||
[[File:Model of human pancreatic islet.jpg|400px]] | [[File:Model of human pancreatic islet.jpg|400px]] | ||
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==Adult Pancreatic Islets== | ==Adult Pancreatic Islets== | ||
[[File:3D_Human_pancreatic_islet.jpg|thumb|Human pancreatic islet in 3D | [[File:3D_Human_pancreatic_islet.jpg|thumb|Human pancreatic islet in 3D{{#pmid:20185817|PMID20185817}}]] | ||
[[File:Pancreas islet - structure human and rat.jpg|thumb|Pancreas islet structure human and rat]] | [[File:Pancreas islet - structure human and rat.jpg|thumb|Pancreas islet structure human and rat]] | ||
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[[File:Human-_pancreatic_adult_islet-glucagon.jpg|200px]] | [[File:Human-_pancreatic_adult_islet-glucagon.jpg|200px]] | ||
* glucagon, mobilizes lipid | * glucagon, mobilizes lipid | ||
===Beta Cells=== | ===Beta Cells=== | ||
[[File:Human-_pancreatic_adult_islet-insulin.jpg|200px]] [[File:Pancreas cartoon.jpg|400px|pancreas structure]] | [[File:Human-_pancreatic_adult_islet-insulin.jpg|200px]] [[File:Pancreas cartoon.jpg|400px|pancreas structure]] | ||
* insulin, increase glucose uptake | * insulin, increase glucose uptake | ||
* stimulate fetal growth, continue to proliferate to postnatal, in infancy most abundant | * stimulate fetal growth, continue to proliferate to postnatal, in infancy most abundant | ||
* amylin - a peptide hormone that is cosecreted with insulin.{{#pmid:31846753|PMID31846753}} | |||
** maternal amylin levels appear to be elevated during pregnancy relative to insulin. | |||
Molecular - '''Nkx6.1''' - NK2 Homeobox 6.1 | |||
* homeobox (Hox) containing transcription factor contain a 60-amino acid evolutionarily conserved DNA-binding homeodomain. | |||
* required for beta cells development and is completely conserved between {{rat}}, {{mouse}}, and human. | |||
:'''Links:''' [[Abnormal_Development_-_Maternal_Diabetes|Maternal Diabetes]] | [http://omim.org/entry/602563 Nkx6.1 OMIM 602563] | |||
===Delta Cells=== | ===Delta Cells=== | ||
* somatostatin, inhibits glucagon, insulin secretion | * somatostatin, inhibits glucagon, insulin secretion | ||
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[[File:Rat-_pancreatic_islet_development.jpg|Rat- pancreatic islet development|500px]] | [[File:Rat-_pancreatic_islet_development.jpg|Rat- pancreatic islet development|500px]] | ||
Rat - pancreatic islet development | Rat - pancreatic islet development{{#pmid:19534767|PMID19534767}} | ||
== | ==Animal Models== | ||
The following species comparison table has been slightly modified from Table 1 data | |||
The following species comparison table has been slightly modified from Table 1 data from a review paper.{{#pmid:20606719|PMID20606719}} | |||
* Islet size is described as an effective diameter of a circle, which depicts the same area as a measured islet area. | * Islet size is described as an effective diameter of a circle, which depicts the same area as a measured islet area. | ||
* β-cell ratio is the area ratio of β-cells in an islet. | * β-cell ratio is the area ratio of β-cells in an islet. | ||
* Both data sets are expressed as the mean value with its standard deviation. | * Both data sets are expressed as the mean value with its standard deviation. | ||
{{Pancreas islet species comparison table}} | |||
===Mouse=== | |||
{| | {| | ||
|- | | [[File:Mouse pancreas cell lineage.jpg|500px]] | ||
| | | The following cell types were collected: {{ME11}} and {{ME15}} pancreatic progenitors, {{ME15}} acinar cells, {{ME15}} endocrine progenitors (EP), {{ME15}}, {{ME17}}, P1, P15, 8–12 week beta cells, P1 and 8–12 week alpha cells, and adult duct cells.{{#pmid:25330008|PMID25330008}} | ||
| | |||
| | * '''Neurog3''' - Neurogenin-3 (Ngn3) protein encoded in humans by the NEUROG3 gene. A basic helix-loop-helix (bHLH) transcription factor expressed in pancreas endocrine progenitor cells. This factor family involved in neural precursor cell determination in the neuroectoderm. [http://omim.org/entry/604882 OMIM 604882] | ||
* '''CD133''' - Prominin-1 a glycoprotein encoded in humans by the PROM1 gene. | |||
* '''CD24''' - Cluster of differentiation 24 or heat stable antigen CD24 (HSA) a protein encoded in humans by the CD24 gene. The protein is a cell adhesion molecule. | |||
* '''CD49f''' - Integrin alpha-6 (ITGA6) protein encoded in humans by the ITGA6 gene. Associates with a beta protein to form a laminin-binding heterodimers involved in adhesion. | |||
|} | |||
==Hormones== | |||
===Insulin=== | |||
* '''Source''' - synthesized by the [[Endocrine_-_Pancreas_Development#Beta_Cells|beta cells]] of the islets of Langerhans. | |||
* '''Protein''' | |||
** 2 dissimilar polypeptide chains, A and B, which are linked by 2 disulphide bonds. | |||
** both chains are derived from a 1-chain precursor, proinsulin. | |||
** proinsulin - converted to insulin by the enzymatic removal of a segment that connects the amino end of the A chain to the carboxyl end of the B chain. | |||
:'''Links:''' [http://omim.org/entry/176730 OMIM] | |||
===Glucagon=== | |||
* '''Source''' - synthesized by the [[Endocrine_-_Pancreas_Development#Alpha_Cells|alpha cells]] of the islets of Langerhans. | |||
* '''Protein''' | |||
** 29-amino acid hormone | |||
** human, rabbit, rat, pig, and cow proteins are identical. | |||
** member of a multigene family that includes - secretin, vasoactive intestinal peptide, gastric inhibitory peptide, glicentin, and others. | |||
* '''Function''' | |||
** counteracts the glucose-lowering action of insulin | |||
** stimulates glycogenolysis and gluconeogenesis. | |||
:'''Links:''' [http://omim.org/entry/138030 OMIM] | |||
==Molecular== | |||
{{Human Pancreas Timeline collapsetable2}} | |||
{| | |||
| '''Mouse Pancreas Cell Lineage''' | |||
In this study{{#pmid:25330008|PMID25330008}} mouse cell types were collected at different ages E11 and E15 pancreatic progenitors, E15 acinar cells, E15 endocrine progenitors (EP), E15, E17, P1, P15, 8–12 week beta cells, P1 and 8–12 week alpha cells, and adult duct cells. The following markers were used in determining the lineages, not both [[Endocrine - Pancreas Development|endocrine]] and [[Gastrointestinal_Tract_-_Pancreas_Development|exocrine]] cells derive from a common precursor. | |||
* '''Neurog3''' - Neurogenin-3 (Ngn3) protein encoded in humans by the NEUROG3 gene. A basic helix-loop-helix (bHLH) transcription factor expressed in pancreas endocrine progenitor cells. This factor family involved in neural precursor cell determination in the neuroectoderm. [http://omim.org/entry/604882 OMIM 604882] | |||
* '''CD133''' - Prominin-1 a glycoprotein encoded in humans by the PROM1 gene. | |||
* '''CD24''' - Cluster of differentiation 24 or heat stable antigen CD24 (HSA) a protein encoded in humans by the CD24 gene. CD24 is a cell adhesion molecule. | |||
* '''CD49f''' - Integrin alpha-6 (ITGA6) protein encoded in humans by the ITGA6 gene. Associates with a beta protein to form a laminin-binding heterodimers involved in adhesion. | |||
| [[File:Mouse pancreas cell lineage.jpg|400px]] | |||
Identification of pancreas cell lineages{{#pmid:25330008|PMID25330008}} | |||
|} | |||
{| | |||
! Developmental Factors | |||
|- | |- | ||
| | | | ||
* '''Pdx1''' - Pancreas/Duodenum Homeobox Protein 1 [http://omim.org/entry/600733 OMIM 600733] | |||
** transcription (transactivator) factor binds the TAAT element in the promoter region of target genes, mainly those involved in pancreas development. | |||
* '''Ngn3''' - Neurogenin3{{#pmid:331178402|PMID331178402}} [http://omim.org/entry/604882 OMIM 604882] | |||
| | ** basic helix-loop-helix transcription factor involved in the determination of neural precursor cells in the neuroectoderm. | ||
* '''NeuroD1''' - Neurogenic Differentiation 1 [http://omim.org/entry/601724 OMIM 601724] | |||
** a basic helix-loop-helix (bHLH) protein that acts as a transcription factors involved in determining cell type during development. | |||
* '''Arx''' - Aristaless-Related Homeobox, X-Linked [http://www.omim.org/entry/300382 OMIM 300382] | |||
** homeobox protein that belongs to the Aristaless-related subset of the paired (Prd) class of homeodomain proteins. | |||
* '''Pax4''' - Paired Box Gene 4 [http://omim.org/entry/167413 OMIM 167413] | |||
** transcription factor containing a paired box domain. | |||
* '''Pax6''' Paired Box Gene 6 [http://omim.org/entry/607108 OMIM 607108] | |||
** transcription factor containing a paired box domain. | |||
* '''Nkx2.2''' - NK2 Homeobox 2 [http://omim.org/entry/604612 OMIM 604612] | |||
** homeobox (Hox) containing transcription factor contain a 60-amino acid evolutionarily conserved DNA-binding homeodomain. | |||
* '''Nkx6.1''' - NK2 Homeobox 6.1 [http://omim.org/entry/602563 OMIM 602563] | |||
** homeobox (Hox) containing transcription factor contain a 60-amino acid evolutionarily conserved DNA-binding homeodomain. | |||
** required for beta cells development and is completely conserved between rat, mouse, and human. | |||
| [[File:Molecular_endocrine_pancreas_cells_01.jpg|400px|alt=Molecular Development of Endocrine Pancreas Cells]] | |||
Molecular Development of Endocrine Pancreas Cells{{#pmid:23940571|PMID23940571}} | |||
| | |||
| | |||
|} | |} | ||
< | :'''Links:''' [[Molecular Development]] | ||
==Pancreas Histology== | |||
<gallery> | |||
File:Pancreas_histology_001.jpg | |||
File:Pancreas_histology_002.jpg | |||
File:Pancreas_histology_003.jpg | |||
File:Pancreas_histology_004.jpg | |||
File:Pancreas_histology_005.jpg | |||
File:Pancreas_histology_101.jpg | |||
File:Pancreas_histology_102.jpg | |||
File:Pancreas_histology_103.jpg | |||
File:Pancreas_histology_104.jpg | |||
File:Pancreas_histology_105.jpg | |||
</gallery> | |||
{{Pancreas Histology Images}} | |||
==Diabetes== | ==Diabetes== | ||
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[[File:Australian trends diabetes prevalence 19990-2008.jpg|500px]] | [[File:Australian trends diabetes prevalence 19990-2008.jpg|500px]] | ||
:'''Links:''' [[Abnormal_Development_-_Maternal_Diabetes|Maternal Diabetes]] | Diabetes is a condition where pancreatic insulin is no longer produced in sufficient required amounts (or at all) meaning that glucose cannot be converted into energy, resulting in health issues related to blood sugar levels. There are two main types: | ||
# '''Type 1 diabetes''' - (10% of all cases) most common chronic childhood condition. An auto-immune condition, where the immune system is activated to destroy the beta cells in the pancreas which produce insulin. Type 1 diabetes is not linked to modifiable lifestyle factors. | |||
# '''Type 2 diabetes''' - (85–90% of all cases) most common in adults. A progressive condition in which the body becomes resistant to the normal effects of insulin and/or gradually loses the capacity to produce enough insulin in the pancreas. Type 2 diabetes is associated with modifiable lifestyle risk factors and has strong genetic and family related risk factors. | |||
Secondary Health Issues: | |||
* '''Diabetic retinopathy''' - is a leading cause of preventable blindness. | |||
* '''Diabetic ketoacidosis''' (DKA) occurs among children and young people with type 1 diabetes and is 1.4 times higher in females. | |||
:'''Links:''' [[Abnormal_Development_-_Maternal_Diabetes|Maternal Diabetes]] | [[#External Links|External Links]] | |||
== Abnormalities == | == Abnormalities == | ||
Listed below are a number of pancreatic developmental abnormalities, see also the 2003 article "Lifetime consequences of abnormal fetal pancreatic development" | Listed below are a number of pancreatic developmental abnormalities, see also the 2003 article "Lifetime consequences of abnormal fetal pancreatic development".{{#pmid:12562919|PMID12562919}} | ||
===Accessory Pancreatic Tissue=== | |||
Pancreatic tissue located in associated gastrointestinal tract tissues/organs such as the wall of the stomach, duodenum, jejunum or Meckel's diverticulum. | |||
===Annular Pancreas=== | |||
Incidence (1 in 7,000 people) pancreas forms as a "ring" of tissue surrounding the duodenum which is subsequently narrowed. | |||
===Diabetes Mellitus=== | |||
Maternal diabetes (and hyperglycaemia) have been shown to lead to increased fetal islet hyperplasia of the insulin producing beta cells and insulin secretion. | |||
===Intrauterine growth restriction=== | |||
Can lead to a delayed development of the insulin producing beta cells and low insulin secretion. | |||
===Tumours=== | |||
Serous Cystadenoma (endocrine tumour), Somatostatinoma (tumour of delta cell origin), intraductal papillary-mucinous neoplasm | |||
===Diabetic ketoacidosis=== | |||
(DKA) occurs among children and young people with type 1 diabetes and is 1.4 times higher in females. | |||
===Hyperinsulinemic hypoglycemia=== | |||
Hyperinsulinemic hypoglycemia (HH) is the unregulated secretion of insulin from the pancreatic β-cells in the presence of low blood glucose levels. Genetic abnormalities in nine genes (ABCC8, KCNJ11, GCK, SCHAD, GLUD1, SLC16A1, HNF1A, HNF4A, and UCP2) have been identified.{{#pmid:27065949|PMID27065949}} | |||
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=== Journals === | === Journals === | ||
* [http://www.pancreasjournal.com/ Pancreas] The official journal of the [http://www.american-pancreatic-association.org/ American Pancreatic Association] and the [http://gakkai.umin.ac.jp/gakkai/gakkai/1999/e_A00030.htm Japan Pancreas Society] | * [http://www.pancreasjournal.com/ Pancreas] The official journal of the [http://www.american-pancreatic-association.org/ American Pancreatic Association] and the [http://gakkai.umin.ac.jp/gakkai/gakkai/1999/e_A00030.htm Japan Pancreas Society] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&term=%22Pancreas%22%5Bjour%5D PubMed] | ||
* [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=JournalHome&ProduktNr=224334 Pancreatology ]Official Journal of the International Association of Pancreatology (IAP); European Pancreatic Club (EPC)and 16 other societies and study groups. | * [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=JournalHome&ProduktNr=224334 Pancreatology ]Official Journal of the International Association of Pancreatology (IAP); European Pancreatic Club (EPC)and 16 other societies and study groups. | ||
* [http://www.joplink.net/ Journal of the Pancreas] electronic journal of pancreatology | * [http://www.joplink.net/ Journal of the Pancreas] electronic journal of pancreatology | ||
* [http://www.diabetologia-journal.org Diabetologia] | [http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&term=%22Diabetologia%22%5Bjour%5D PubMed] | |||
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File:Bailey273.jpg|Fig. 273. From a model of the duodenum and the primary evaginations of the liver and pancreas in a 5 mm sheep embryo | |||
File:Bailey274.jpg|Fig. 274. From a reconstruction of the anlagen of the liver and pancreas and a part of the stomach and duodenum of a human embryo of 4 weeks | |||
File:Bailey275.jpg|Fig. 275. From a reconstruction of the anlagen of the liver and pancreas and the stomach of a human embryo of 8 mm | |||
File:Bailey278 279.jpg|Figs. 278 and 279. From models of the developing liver and pancreas of rabbit embryos | |||
File:Bailey280.jpg|Fig. 280. From a transverse section through the region of the duodenum of a pig embryo of 14 mm | |||
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==External Links== | |||
{{External Links}} | |||
* '''F1000 Reports''' - [http://f1000.com/reports/b/2/17/ Recent advances in pancreas development] | |||
* '''Howard Hughes Medical Institute''' - [http://seungkimlab.stanford.edu Seung Kim Lab] | |||
* Australian Institute of Health and Welfare - [Factsheet - Diabetic ketoacidosis (DKA) among children and young people with type 1 diabetes] | |||
* Diabetes Australia - [https://www.diabetesaustralia.com.au/type-1-diabetes Type 1 Diabetes] | [https://www.diabetesaustralia.com.au/type-2-diabetes Type 2 Diabetes] | |||
{{Glossary}} | |||
{{ | {{Footer}} | ||
[[Category:Endocrine]] [[Category:Pancreas]] | [[Category:Endocrine]] [[Category:Pancreas]] |
Latest revision as of 23:10, 7 January 2020
Embryology - 25 May 2024 ![]() ![]() ![]() |
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Introduction
![](/embryology/images/thumb/5/5e/Human-_pancreatic_adult_islet.jpg/350px-Human-_pancreatic_adult_islet.jpg)
The pancreas is a two-headed organ, not only in origin but also in function. In origin, the pancreas develops from two separate primordia. In function, the organ has both endocrine function in relation to regulating blood glucose (and also other hormone secretions) and gastrointestinal function as an exocrine (digestive) organ, see exocrine pancreas.
In recent years there has been much research due to the increasing incidence of diabetes in humans and the potential for stem cell therapeutics. Much is now known about the epithelial/mesenchymal and molecular regulation of pancres development.
At the foregut/midgut junction the septum transversum generates 2 pancreatic buds (dorsal and ventral endoderm) which will fuse to form the pancreas. The dorsal bud arises first and generates most of the pancreas. The ventral bud arises beside the bile duct and forms only part of the head and uncinate process of the pancreas.
In the fetal period islet cell clusters (icc) differentiate from pancreatic bud endoderm. These cell clusters form acini and ducts (exocrine). On the edge of these cell clusters pancreatic islets (endocrine) also form. Pancreatic hormonal function is mainly to secrete insulin and glucagon that together regulate blood glucose levels. Pancreatic progenitor cells give rise to five endocrine cell types secreting: insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. Furthermore gastrin, secreted by stomach G-cells, is also embryonically expressed in the pancreas but disappears after birth.[2]
The pancreas exocrine function begins after birth, while the endocrine function (hormone release) can be measured from 10 to 15 weeks onward. At this stage, it is not clear what the exact roles of these hormones are in regulating fetal growth.
- Functions - exocrine (amylase, alpha-fetoprotein), 99% by volume; endocrine (pancreatic islets) 1% by volume about 1 million islets
- Exocrine function - begins after birth
- Endocrine function - from 10 to 15 weeks onward hormone release
- exact roles of hormones in regulating fetal growth?
- Links: Endocrine Pancreas | Exocrine Pancreas
See also: Lecture - Gastrointestinal Development | Maternal Diabetes
Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Pancreas Embryology | Pancreas Development | Endocrine Pancreas Development | Exocrine Pancreas Development | pancreatic islet |
Older papers |
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These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
See also the Discussion Page for other references listed by year and References on this current page.
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Pancreas Development
- Pancreatic buds - duodenal level endoderm, splanchnic mesoderm forms dorsal and ventral mesentery, dorsal bud (larger, first), ventral bud (smaller, later)
- Pancreas Endoderm - pancreas may be opposite of liver
- Heart cells promote/notochord prevents liver formation
- Notochord may promote pancreas formation
- Heart may block pancreas formation
- Duodenum growth/rotation - brings ventral and dorsal buds together, fusion of buds
- Pancreatic duct - ventral bud duct and distal part of dorsal bud, exocrine function
- Islet cells - cords of endodermal cells form ducts, from which cells bud off to form islets[9]
Human Pancreas Timeline
Carnegie Stage | Days | Event |
---|---|---|
10 | 25-27 | distal endoderm foregut |
12 | 29-31 | pancreatic duodenal endoderm
extra-hepatic billiard duct |
13 | 30-33 | pancreatic bud |
19 | 47 | "trunk" progenitor
"tip" progenitor |
23 | 8 weeks + | fetal beta cell
ductal cell |
fetal | 14 weeks | acinar cell |
Table data[10] Links: pancreas | exocrine pancreas | pancreas molecular timeline | timeline |
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Human (week 4) pancreatic buds | Human (week 8, Stage 22) pancreas |
- Week 7 to 20 - pancreatic hormones secretion increases, small amount maternal insulin
- Week 10 - glucagon (alpha) differentiate first, somatostatin (delta), insulin (beta) cells differentiate, insulin secretion begins
- Week 15 - glucagon detectable in fetal plasma
Mouse pancreas duct development cartoon
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Pig embryo (14 mm CRL) (ventral and dorsal)
Fetal Pancreas
Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries.[11]
A diagram showing joining processes between the dorsal and ventral primordia of the pancreas as well as the hypothetical rotation of the duodenum along a left-right axis. Viewed from the posterosuperior side of the body. A horizontal plane including most parts of the duodenum is shown to emphasize, in contrast to adults, the course of the second portion (D2) directing posteriorly rather than inferiorly.
Developing Pancreatic Islets
Model of endocrine cell and vessel organization in human islets[12] | A α-Cells (green) and β-cells (red) are organized into a thick folded plate lined at both sides with vessels (blue).
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Adult Pancreatic Islets
![](/embryology/images/thumb/7/73/3D_Human_pancreatic_islet.jpg/300px-3D_Human_pancreatic_islet.jpg)
The adult pancreatic islets (Islets of Langerhans) contain four distinct endocrine cell types.
Alpha Cells
- glucagon, mobilizes lipid
Beta Cells
- insulin, increase glucose uptake
- stimulate fetal growth, continue to proliferate to postnatal, in infancy most abundant
- amylin - a peptide hormone that is cosecreted with insulin.[13]
- maternal amylin levels appear to be elevated during pregnancy relative to insulin.
Molecular - Nkx6.1 - NK2 Homeobox 6.1
- homeobox (Hox) containing transcription factor contain a 60-amino acid evolutionarily conserved DNA-binding homeodomain.
- required for beta cells development and is completely conserved between rat, mouse, and human.
- Links: Maternal Diabetes | Nkx6.1 OMIM 602563
Delta Cells
- somatostatin, inhibits glucagon, insulin secretion
F-cells
- pancreatic polypeptide
Rat - pancreatic islet development[14]
Animal Models
The following species comparison table has been slightly modified from Table 1 data from a review paper.[15]
- Islet size is described as an effective diameter of a circle, which depicts the same area as a measured islet area.
- β-cell ratio is the area ratio of β-cells in an islet.
- Both data sets are expressed as the mean value with its standard deviation.
Pancreas Islet Species Comparison | |||
---|---|---|---|
Species | Age | Islet size (μm) | β-cell ratio |
Human | 39 years (adult) | 50 ± 29 | 0.64 ± 0.21 |
Monkey | 1 year | 67 ± 38* | 0.79 ± 0.14* |
Pig | 6 month | 49 ± 15a | 0.89 ± 0.11* |
Rabbit | 6 month | 64 ± 28* | 0.79 ± 0.17* |
Bird | 40 day | 24 ± 6* | 0.46 ± 0.24* |
Wild-type mouse | 6 month | 116 ± 80* | 0.85 ± 0.14* |
Pregnant mouse | 3 month | 112 ± 94* | 0.84 ± 0.22* |
ob/ob mouse | 15 week | 86 ± 76* | 0.92 ± 0.11* |
db/db mouse | 15 week | 47 ± 24b | 0.53 ± 0.24c |
*p < 0.0001 ap = 0.65 bp = 0.42 cp = 0.0004 compared with human.
| |||
Reference: [15] |
Mouse
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The following cell types were collected: E11 and E15 pancreatic progenitors, E15 acinar cells, E15 endocrine progenitors (EP), E15, E17, P1, P15, 8–12 week beta cells, P1 and 8–12 week alpha cells, and adult duct cells.[16]
|
Hormones
Insulin
- Source - synthesized by the beta cells of the islets of Langerhans.
- Protein
- 2 dissimilar polypeptide chains, A and B, which are linked by 2 disulphide bonds.
- both chains are derived from a 1-chain precursor, proinsulin.
- proinsulin - converted to insulin by the enzymatic removal of a segment that connects the amino end of the A chain to the carboxyl end of the B chain.
- Links: OMIM
Glucagon
- Source - synthesized by the alpha cells of the islets of Langerhans.
- Protein
- 29-amino acid hormone
- human, rabbit, rat, pig, and cow proteins are identical.
- member of a multigene family that includes - secretin, vasoactive intestinal peptide, gastric inhibitory peptide, glicentin, and others.
- Function
- counteracts the glucose-lowering action of insulin
- stimulates glycogenolysis and gluconeogenesis.
- Links: OMIM
Molecular
Human Pancreas Molecular Timeline | |||||||||||||||||||||||||||||||
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Mouse Pancreas Cell Lineage
In this study[16] mouse cell types were collected at different ages E11 and E15 pancreatic progenitors, E15 acinar cells, E15 endocrine progenitors (EP), E15, E17, P1, P15, 8–12 week beta cells, P1 and 8–12 week alpha cells, and adult duct cells. The following markers were used in determining the lineages, not both endocrine and exocrine cells derive from a common precursor.
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![]() Identification of pancreas cell lineages[16] |
Developmental Factors | |
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![]() Molecular Development of Endocrine Pancreas Cells[2] |
- Links: Molecular Development
Pancreas Histology
- Pancreas Histology Links: overview (label) | exocrine (label) | endocrine (label) | blood vessels (label) | insulin (label) | overview | exocrine | endocrine | blood vessels | insulin | Islet labeled for insulin and Glucagon | Insulin (Fl) | Glucagon (Fl) | GIT Histology
Diabetes
Diabetes is a condition where pancreatic insulin is no longer produced in sufficient required amounts (or at all) meaning that glucose cannot be converted into energy, resulting in health issues related to blood sugar levels. There are two main types:
- Type 1 diabetes - (10% of all cases) most common chronic childhood condition. An auto-immune condition, where the immune system is activated to destroy the beta cells in the pancreas which produce insulin. Type 1 diabetes is not linked to modifiable lifestyle factors.
- Type 2 diabetes - (85–90% of all cases) most common in adults. A progressive condition in which the body becomes resistant to the normal effects of insulin and/or gradually loses the capacity to produce enough insulin in the pancreas. Type 2 diabetes is associated with modifiable lifestyle risk factors and has strong genetic and family related risk factors.
Secondary Health Issues:
- Diabetic retinopathy - is a leading cause of preventable blindness.
- Diabetic ketoacidosis (DKA) occurs among children and young people with type 1 diabetes and is 1.4 times higher in females.
- Links: Maternal Diabetes | External Links
Abnormalities
Listed below are a number of pancreatic developmental abnormalities, see also the 2003 article "Lifetime consequences of abnormal fetal pancreatic development".[17]
Accessory Pancreatic Tissue
Pancreatic tissue located in associated gastrointestinal tract tissues/organs such as the wall of the stomach, duodenum, jejunum or Meckel's diverticulum.
Annular Pancreas
Incidence (1 in 7,000 people) pancreas forms as a "ring" of tissue surrounding the duodenum which is subsequently narrowed.
Diabetes Mellitus
Maternal diabetes (and hyperglycaemia) have been shown to lead to increased fetal islet hyperplasia of the insulin producing beta cells and insulin secretion.
Intrauterine growth restriction
Can lead to a delayed development of the insulin producing beta cells and low insulin secretion.
Tumours
Serous Cystadenoma (endocrine tumour), Somatostatinoma (tumour of delta cell origin), intraductal papillary-mucinous neoplasm
Diabetic ketoacidosis
(DKA) occurs among children and young people with type 1 diabetes and is 1.4 times higher in females.
Hyperinsulinemic hypoglycemia
Hyperinsulinemic hypoglycemia (HH) is the unregulated secretion of insulin from the pancreatic β-cells in the presence of low blood glucose levels. Genetic abnormalities in nine genes (ABCC8, KCNJ11, GCK, SCHAD, GLUD1, SLC16A1, HNF1A, HNF4A, and UCP2) have been identified.[18]
References
- ↑ Scharfmann R, Xiao X, Heimberg H, Mallet J & Ravassard P. (2008). Beta cells within single human islets originate from multiple progenitors. PLoS ONE , 3, e3559. PMID: 18958289 DOI.
- ↑ 2.0 2.1 2.2 2.3 Suissa Y, Magenheim J, Stolovich-Rain M, Hija A, Collombat P, Mansouri A, Sussel L, Sosa-Pineda B, McCracken K, Wells JM, Heller RS, Dor Y & Glaser B. (2013). Gastrin: a distinct fate of neurogenin3 positive progenitor cells in the embryonic pancreas. PLoS ONE , 8, e70397. PMID: 23940571 DOI.
- ↑ Ryu GR, Lee E, Kim JJ, Moon SD, Ko SH, Ahn YB & Song KH. (2018). Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation. PLoS ONE , 13, e0206401. PMID: 30379923 DOI.
- ↑ Scavuzzo MA, Hill MC, Chmielowiec J, Yang D, Teaw J, Sheng K, Kong Y, Bettini M, Zong C, Martin JF & Borowiak M. (2018). Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis. Nat Commun , 9, 3356. PMID: 30135482 DOI.
- ↑ Vieira A, Vergoni B, Courtney M, Druelle N, Gjernes E, Hadzic B, Avolio F, Napolitano T, Navarro Sanz S, Mansouri A & Collombat P. (2018). Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity. PLoS ONE , 13, e0201536. PMID: 30092080 DOI.
- ↑ Rovira M, Huang W, Yusuff S, Shim JS, Ferrante AA, Liu JO & Parsons MJ. (2011). Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation. Proc. Natl. Acad. Sci. U.S.A. , 108, 19264-9. PMID: 22084084 DOI.
- ↑ Landsman L, Nijagal A, Whitchurch TJ, Vanderlaan RL, Zimmer WE, Mackenzie TC & Hebrok M. (2011). Pancreatic mesenchyme regulates epithelial organogenesis throughout development. PLoS Biol. , 9, e1001143. PMID: 21909240 DOI.
- ↑ Dames P, Puff R, Weise M, Parhofer KG, Göke B, Götz M, Graw J, Favor J & Lechner A. (2010). Relative roles of the different Pax6 domains for pancreatic alpha cell development. BMC Dev. Biol. , 10, 39. PMID: 20377917 DOI.
- ↑ Suckale J & Solimena M. (2008). Pancreas islets in metabolic signaling--focus on the beta-cell. Front. Biosci. , 13, 7156-71. PMID: 18508724
- ↑ 10.0 10.1 Jennings RE, Berry AA, Kirkwood-Wilson R, Roberts NA, Hearn T, Salisbury RJ, Blaylock J, Piper Hanley K & Hanley NA. (2013). Development of the human pancreas from foregut to endocrine commitment. Diabetes , 62, 3514-22. PMID: 23630303 DOI.
- ↑ Jin ZW, Yu HC, Cho BH, Kim HT, Kimura W, Fujimiya M & Murakami G. (2010). Fetal topographical anatomy of the pancreatic head and duodenum with special reference to courses of the pancreaticoduodenal arteries. Yonsei Med. J. , 51, 398-406. PMID: 20376893 DOI.
- ↑ 12.0 12.1 Bosco D, Armanet M, Morel P, Niclauss N, Sgroi A, Muller YD, Giovannoni L, Parnaud G & Berney T. (2010). Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes , 59, 1202-10. PMID: 20185817 DOI.
- ↑ Boyle CN & Le Foll C. (2019). Amylin and Leptin interaction: Role During Pregnancy, Lactation and Neonatal Development. Neuroscience , , . PMID: 31846753 DOI.
- ↑ Cabrera-Vásquez S, Navarro-Tableros V, Sánchez-Soto C, Gutiérrez-Ospina G & Hiriart M. (2009). Remodelling sympathetic innervation in rat pancreatic islets ontogeny. BMC Dev. Biol. , 9, 34. PMID: 19534767 DOI.
- ↑ 15.0 15.1 Kim A, Miller K, Jo J, Kilimnik G, Wojcik P & Hara M. (2009). Islet architecture: A comparative study. Islets , 1, 129-36. PMID: 20606719 DOI.
- ↑ 16.0 16.1 16.2 Benitez CM, Qu K, Sugiyama T, Pauerstein PT, Liu Y, Tsai J, Gu X, Ghodasara A, Arda HE, Zhang J, Dekker JD, Tucker HO, Chang HY & Kim SK. (2014). An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development. PLoS Genet. , 10, e1004645. PMID: 25330008 DOI.
- ↑ Holemans K, Aerts L & Van Assche FA. (2003). Lifetime consequences of abnormal fetal pancreatic development. J. Physiol. (Lond.) , 547, 11-20. PMID: 12562919 DOI.
- ↑ Nessa A, Rahman SA & Hussain K. (2016). Hyperinsulinemic Hypoglycemia - The Molecular Mechanisms. Front Endocrinol (Lausanne) , 7, 29. PMID: 27065949 DOI.
Journals
- Pancreas The official journal of the American Pancreatic Association and the Japan Pancreas Society | PubMed
- Pancreatology Official Journal of the International Association of Pancreatology (IAP); European Pancreatic Club (EPC)and 16 other societies and study groups.
- Journal of the Pancreas electronic journal of pancreatology
- Diabetologia | PubMed
Online Textbooks
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents
NIH Genes & Disease Chapter 41 - Endocrine
Pathophysiology of the Endocrine System The Endocrine Pancreas
Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. table 15-1. Some Hormone-induced Cell Responses Mediated by Cyclic AMP
Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct.
Search NLM Online Textbooks- "pancreas development" : Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach
Search Bookshelf Pancreas Development
Reviews
Honoré C, Rescan C, Hald J, McGrath PS, Petersen MB, Hansson M, Klein T, Østergaard S, Wells JM & Madsen OD. (2016). Revisiting the immunocytochemical detection of Neurogenin 3 expression in mouse and man. Diabetes Obes Metab , 18 Suppl 1, 10-22. PMID: 27615127 DOI.
Ranjan AK, Joglekar MV & Hardikar AA. (2009). Endothelial cells in pancreatic islet development and function. Islets , 1, 2-9. PMID: 21084843 DOI.
Kinkel MD & Prince VE. (2009). On the diabetic menu: zebrafish as a model for pancreas development and function. Bioessays , 31, 139-52. PMID: 19204986 DOI.
Gittes GK. (2009). Developmental biology of the pancreas: a comprehensive review. Dev. Biol. , 326, 4-35. PMID: 19013144 DOI.
Bonal C & Herrera PL. (2008). Genes controlling pancreas ontogeny. Int. J. Dev. Biol. , 52, 823-35. PMID: 18956314 DOI.
Oliver-Krasinski JM & Stoffers DA. (2008). On the origin of the beta cell. Genes Dev. , 22, 1998-2021. PMID: 18676806 DOI.
Articles
Portha B, Chavey A & Movassat J. (2011). Early-life origins of type 2 diabetes: fetal programming of the beta-cell mass. Exp Diabetes Res , 2011, 105076. PMID: 22110471 DOI.
Riedel MJ, Asadi A, Wang R, Ao Z, Warnock GL & Kieffer TJ. (2012). Immunohistochemical characterisation of cells co-producing insulin and glucagon in the developing human pancreas. Diabetologia , 55, 372-81. PMID: 22038519 DOI.
Ma F, Haumaitre C, Chen F & Han Z. (2011). Comparison of murine embryonic pancreatic development in vitro and in vivo. Pancreas , 40, 1012-7. PMID: 21926540 DOI.
McDonald E, Li J, Krishnamurthy M, Fellows GF, Goodyer CG & Wang R. (2012). SOX9 regulates endocrine cell differentiation during human fetal pancreas development. Int. J. Biochem. Cell Biol. , 44, 72-83. PMID: 21983268 DOI.
Yang KM, Yong W, Li AD & Yang HJ. (2011). Insulin-producing cells are bi-potential and differentiatorsprior to proliferation in early human development. World J Diabetes , 2, 54-8. PMID: 21537461 DOI.
Meier JJ, Köhler CU, Alkhatib B, Sergi C, Junker T, Klein HH, Schmidt WE & Fritsch H. (2010). Beta-cell development and turnover during prenatal life in humans. Eur. J. Endocrinol. , 162, 559-68. PMID: 20022941 DOI.
Jeon J, Correa-Medina M, Ricordi C, Edlund H & Diez JA. (2009). Endocrine cell clustering during human pancreas development. J. Histochem. Cytochem. , 57, 811-24. PMID: 19365093 DOI.
Oliver-Krasinski JM, Kasner MT, Yang J, Crutchlow MF, Rustgi AK, Kaestner KH & Stoffers DA. (2009). The diabetes gene Pdx1 regulates the transcriptional network of pancreatic endocrine progenitor cells in mice. J. Clin. Invest. , 119, 1888-98. PMID: 19487809 DOI.
Eberhard D, Tosh D & Slack JM. (2008). Origin of pancreatic endocrine cells from biliary duct epithelium. Cell. Mol. Life Sci. , 65, 3467-80. PMID: 18810318 DOI.
Scharfmann R, Xiao X, Heimberg H, Mallet J & Ravassard P. (2008). Beta cells within single human islets originate from multiple progenitors. PLoS ONE , 3, e3559. PMID: 18958289 DOI.
Piper K, Brickwood S, Turnpenny LW, Cameron IT, Ball SG, Wilson DI & Hanley NA. (2004). Beta cell differentiation during early human pancreas development. J. Endocrinol. , 181, 11-23. PMID: 15072563
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Additional Images
Historic Images
External Links
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- F1000 Reports - Recent advances in pancreas development
- Howard Hughes Medical Institute - Seung Kim Lab
- Australian Institute of Health and Welfare - [Factsheet - Diabetic ketoacidosis (DKA) among children and young people with type 1 diabetes]
- Diabetes Australia - Type 1 Diabetes | Type 2 Diabetes
Glossary Links
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Cite this page: Hill, M.A. (2024, May 25) Embryology Endocrine - Pancreas Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Pancreas_Development
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G