Endocrine - Pancreas Development

Embryology - 3 Dec 2023        Expand to Translate
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Introduction

Human Pancreatic Islets (Islets of Langerhans)

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.

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.

Pancreas adult

• 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

Historic Embryology: 1912 Pancreas Development | 1930 Ventral Pancreas

Some Recent Findings

Molecular Development of Endocrine Pancreas CellsMolecular Pancreas

Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation "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." Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis "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 eE14.5 and eE16.5 mouse pancreas. While eE14.5 and eE16.5 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 eE14.5 EPs: eE16.5 EPs have a higher propensity to form beta cells. Analysis of eE14.5 and eE16.5 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 "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."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. 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

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. Gastrin: a distinct fate of neurogenin3 positive progenitor cells in the embryonic pancreas "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 "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 "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. "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."

Pancreas Development

Pancreatic buds and duct developing

• 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

Human Pancreas Timeline

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   Links: pancreas | exocrine pancreas | pancreas molecular timeline | timeline

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

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.

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

A α-Cells (green) and β-cells (red) are organized into a thick folded plate lined at both sides with vessels (blue). α-Cells are mostly at the periphery of the plate and in close contact with vessels. β-Cells occupy a more central part of the plate and most of them develop cytoplasmic extension that runs between α-cells and reaches the surface of vessels. B The plate with adjacent vessels is folded so that it forms an islet. (Text based on original reference legend)

Adult Pancreatic Islets

Human pancreatic islet in 3D

Pancreas islet structure human and rat

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.
  • 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

Animal Models

The following species comparison table has been slightly modified from Table 1 data from a review paper.

• 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. 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.
Reference:

Mouse

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. 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. 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 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

Human Pancreas Timeline Carnegie Stage Days Molecular Event 10 25-27 FOXA2, SOX17 (dorsal), SHH (ventral) distal endoderm foregut 12 29-31 PDX1, FOXA2, SOX17, GATA4, SOX9 (weak) SOX9, FOXA2, PDX1 (weak) pancreatic duodenal endoderm extra-hepatic billiard duct 13 30-33 PDX1, FOXA2, GATA4, NKX6.1, SOX9 pancreatic bud 19 47 PDX1, FOXA2, GATA4, NKX6.1, SOX9 PDX1, FOXA2, GATA4, NKX6.1, SOX9 "trunk" progenitor "tip" progenitor 23 8 weeks + PDX1, FOXA2, GATA4, NKX6.1, NKX2.2, ISL1 SOX9, FOXA2, PDX1 (weak) fetal beta cell ductal cell fetal 14 weeks GATA4 acini cell   Table data   Links: pancreas | exocrine pancreas | timeline

Mouse Pancreas Cell Lineage In this study 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. 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. 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.

Identification of pancreas cell lineages

Developmental Factors

Pdx1 - Pancreas/Duodenum Homeobox Protein 1 OMIM 600733 transcription (transactivator) factor binds the TAAT element in the promoter region of target genes, mainly those involved in pancreas development. Ngn3 - Neurogenin3PubmedParser error: Pubmed did not return article data, please check the PMID or try again later. (PMID: 331178402) OMIM 604882 basic helix-loop-helix transcription factor involved in the determination of neural precursor cells in the neuroectoderm. NeuroD1 - Neurogenic Differentiation 1 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 OMIM 300382 homeobox protein that belongs to the Aristaless-related subset of the paired (Prd) class of homeodomain proteins. Pax4 - Paired Box Gene 4 OMIM 167413 transcription factor containing a paired box domain. Pax6 Paired Box Gene 6 OMIM 607108 transcription factor containing a paired box domain. Nkx2.2 - NK2 Homeobox 2 OMIM 604612 homeobox (Hox) containing transcription factor contain a 60-amino acid evolutionarily conserved DNA-binding homeodomain. Nkx6.1 - NK2 Homeobox 6.1 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.

Molecular Development of Endocrine Pancreas Cells

Links: Molecular Development

Pancreas Histology

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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:

1. 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.
2. 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".

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.

Links: NIH Genes and Disease Chapter 41 - Endocrine | Medline Plus - Annular Pancreas |

References

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

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  Human - Pancreatic islet

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  Rat - pancreatic islet development

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  Pancreas_islet - structure human and rat

Historic Images

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  Fig. 273. From a model of the duodenum and the primary evaginations of the liver and pancreas in a 5 mm sheep embryo

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  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

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  Fig. 275. From a reconstruction of the anlagen of the liver and pancreas and the stomach of a human embryo of 8 mm

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  Figs. 278 and 279. From models of the developing liver and pancreas of rabbit embryos

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  Fig. 280. From a transverse section through the region of the duodenum of a pig embryo of 14 mm

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. (2023, December 3) Embryology Endocrine - Pancreas Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Pancreas_Development

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G