Endocrine - Pancreas Development

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Notice - Mark Hill

Currently this page is only a template and will be updated (this notice removed when completed).

Introduction

Pancreatic Islet Development (rat)

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 exocrine (digestive) and endocrine functions in relation to regulating blood glucose and also other hormone secretions.

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 pancratic 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 to secrete insulin and glucagon which together regulate blood glucose levels and also somaostatin.

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

pancreas structure

Historic Embryology - Endocrine
1903 Islets of Langerhans \| 1903 Pig Adrenal \| 1904 interstitial Cells \| 1908 Pancreas Different Species \| 1908 Pituitary \| 1908 Pituitary histology \| 1911 Rathke's pouch \| 1912 Suprarenal Bodies \| 1914 Suprarenal Organs \| 1915 Pharynx \| 1916 Thyroid \| 1918 Rabbit Hypophysis \| 1920 Adrenal \| 1935 Mammalian Hypophysis \| 1926 Human Hypophysis \| 1927 Adrenal \| 1927 Hypophyseal fossa \| 1930 Adrenal \| 1932 Pineal Gland and Cysts \| 1935 Hypophysis \| 1935 Pineal \| 1937 Pineal \| 1935 Parathyroid \| 1940 Adrenal \| 1941 Thyroid \| 1950 Thyroid Parathyroid Thymus \| 1957 Adrenal

| Lecture- Gastrointestinal Tract Development | original page

Functions - exocrine (amylase, alpha-fetoprotein), 99% by volume; endocrine (pancreatic islets) 1% by volume
Exocrine function - begins after birth
Endocrine function - from 10 to 15 weeks onward hormone release
- exact roles of hormones in regulating fetal growth?

Some Recent Findings

Relative roles of the different Pax6 domains for pancreatic alpha cell development.^[1] "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

Stage22 pancreas

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

Pancreatic Islets

Rat- pancreatic islet development

Islets of Langerhans - 4 endocrine cell types
Alpha - glucagon, mobilizes lipid
Beta - insulin, increase glucose uptake
- Beta cells, stimulate fetal growth, continue to proliferate to postnatal, in infancy most abundant
Delta - somatostatin, inhibits glucagon, insulin secretion
F-cells - pancreatic polypeptide

Pancreas Timeline

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