Week 1: Endocrine Pancreas and enteroendocrine cells

Question 1

Embryology of pancreas

Answer 1

• develops at 4th week. 2 outpocketings from dorsal and ventral embryonic duodenum
• derived from endoderm
• ventral: duct of Wirsung. Becomes major duct that pancreas drains through, to major papilla
• dorsal: duct of santorini, connects so duodenum. Fuses with ventral duct, can persist as minor duct to drain through lesser papilla or as blind accessory duct

Question 2

Endocrine pancreas: structure

Answer 2

• islets of Langerhans, scattered throughout. Make up 1-2% of volume
• each islet is surrounded by connective tissue capsule. Arterioles give rise to network of fenestrated capillaires that penetrate islet from periphery. Endocrine cells secrete basolaterally where the capillary is.
• capillaries perfuse a and d cells first, before reaching b cells, centrally.
• islet cell secretion have regulatory effects on acing cells of exocrine pancreas
• islet has richer vascular supply than surrounding exocrine glands

Question 3

Principal cell types of Islet

Answer 3

1. a cell: 15-20% of islet population. Peripheral. Glucagon secretion. 250 nm granules, more densely packed than b cells
2. b cells: 70%. central. insulin secretion. 300nm secretory granules, dense polyhedral core and pale matrix.
3. d cells: 5-10%. peripheral. Secret somatostatin. 300-350nm secretory granules. low to medium electron density.

Question 4

Functions of insulin

Answer 4

1. synthesis of glycogen, stored in liver and muscle
2. stimulates synthesis and storage of fats in fat depots and in liver. inhibits fat release.
3. stimulates protein synthesis for repair and growth of cells
   - insulin is released in response to glucagon release, temporal offset.

Question 5

Functions of glucagon

Answer 5

• release of glucose into blood stream
• gluconeogensis
• breakdown of glycogen in the liver
• mobilization of fats from adipose cells

Question 6

functions of somatostatin

Answer 6

• inhibits both b and a cells, inhibits insulin and glucagon secretion
• secreted in response to high levels of the endocrine hormones

Question 7

Structure of insulin secretory granules

Answer 7

• dense core: crystal, 3 insulin: 1 Zn2+
• halo: peptide, small molecules, ions
• immediate resolution of halo part, then dense core takes some time to dissolve after release

Question 8

Regulation of islet activity

Answer 8

1. blood glucose levels
   >70mg/100mL stimulate b cells to release insulin
   <70mg/100mL stimulate a cells to release glucagon
2. Hormones:
   -GLP-1 (glucagon like protein): recreated by L cells from gut mucosa. augments insulin secretion
   -release of glucagon stimulates neighboring b cells to compensate by securing insulin
   -somatostatin inhibits both
3. Autonomic innervation: 10% of islet cells have nerve endings on plasma membrane
   -parasymp: increases insulin and glucagon secretion
   -sympathetic: increases glucagon but inhibits insulin release

Question 9

loss of beta cells due to dedifferentiation

Answer 9

• FoxO1 localizes to cytoplasm in normoglycemic
• in mild hyperglycemia: FoxO1 localizes partially to nucleus
• in severe hyperglycemia: FoxO1 is absent in the dedifferentiated beta cell

Question 10

Enteroendocrine cells of the gut

Answer 10

Ingested food evokes satiation by
1. gastric distension
2. peptides released from enteroendocrine cells
possible MECHANISMs
-cellular uptake and intracellular metabolism of glucose
-taste receptors in signaling cascade similar to that for taste sensation in taste bud