DSA Endocrine Pancreas Flashcards
development of the pancreas
a. By week 4, 2 outpocketings of the endoderm of the duodenum develop as ventral and dorsal pancreas each with own dust
i. Ventral pancreashead and associates with common bile duct
ii. Dorsal pancreasforms part of head, body, tail of pancreas
b. By week 12—pancreatic acini develop from ducts
c. Endocrine and exocrine develop at same time but endocrine cells are first observed at base of differentiating exocrine acini by weeks 12-16
2 parts of pancreas
i. Exocrine—acini involved in the synthesis and secretion of several digestive enzymes transported by a duct system into the duodenum
ii. Endocrine—formed by islets of langerhans scattered throughout the pancreas
2 parts of the islets of Langerhans
a. vascular part—insuloacinar portal system
i. consists of afferent arteriole giving rise to a capillary network lined by fenestrated endothelial cells
ii. venules leaving the islets of Langerhans supply blood to adjacent pancreatic acini
iii. enables local action of insular Hs on exocrine pancreas
1. independent vascular system—acini vascular system—supplies blood directly to exocrine pancreatic acini
b. anastomosing cords of endocrine cells—A, B, D, and F cells each secrete a single H
A cells of pancreas-
release glucagon
- Glucagon is a 29 AA peptide stored in granules released by exocytosis when there is a dec in the levels of glucose
- Glucagon increases blood glucose levels in increasing hepatic glycogenolysis
- Glucagon binds to specific membrane bound receptors and results in synthesis of cAMP
- Glucagon is derived from preproglucagon
- Glucagon is found in the GI tract, brain, and pancreas
a. Circulating glucagon from the pancreas and GI is taken to the liver and degraded
b. Glucagon induces hyperglycemia by is glycogenolytic activity on hepatocytes - Secretion of glucagon is stimulated by:
a. Fall in conc of glucose in blood
b. Inc in arginine and alanine in serum
c. Stimulation of SNS
B cells of pancreas
secrete insulin
- Insulin is a polypeptide consisting of 2 chains of
- Insulin is derived from preproinsulin which is synthesized in the RER and processed in golgi
a. Preproinsulin gives rise to proinsulin in which C peptide connects the 2 chains
b. Removal of C peptide results in:
i. Separation of chains A and B
ii. Organization of a crystalline core consisting of a hexamer and zinc atoms
BP and insulin
- Increase in blood pressure stimulates the release of both insulin and C peptide stored in secretory granules
GLUT2 and insulin
- Glucose is taken up by B cells by an insulin-independent glucose transporter protein (GLUT2) and stored insulin is released in Ca dependent manner
a. If glucose levels remain high, new synthesis of insulin occurs and GLUT 2 is present in hepatocytes
how does insulin inc the transport of glucose into cells?
a. Transmembrane transport of glucose and AAs
b. Formation of glycogen in hepatocytes and skeletal/cardiac M cells
c. Conversion of glucose to triglycerides
alpha subunit of insulin R
- Insulin initiates its effect by binding ot the alpha subunit of its receptor
a. Insulin receptor has an alpha and beta subunit
i. Intracellular domain of the beta subunit has tyrosine kinase activity—autophosphorylates and triggers intracellular responses
ii. One response is the translocation of glucose transporter protein 4 (GLUT4) from the golgi to the plasma membrane to facilitate the uptake of glucose
iii. GLUT4 is insulin dependent and is present in adipocytes and skeletal/cardiac muscle
differences b/w GLUT2 and 4
i. GLUT2—insulin independent and serves to transport glucose to insular B cells and hepatocytes
ii. GLUT4—insulin dependent and serves to remove glucose from blood
D cells of the pancreas
i. gastrin and somatostatin
1. Somatostatin—same as that produced in hypothalamus
a. Inhibits release of insulin and glucagon
b. Also inhibits HCl release by parietal cells of the fundus, inhibits release of gastrin from enteroendocrine cells, secretion of pancreatic bicarb and enzymes, and inhibits contraction of the gallbladder
c. Inhibits release of GH from anterior pituitary
F cells of the pancreas
i. pancreatic polypeptide
1. Inhibits the release of somatostatin
2. Also inhibits the secretion of pancreatic enzymes and blocks the secretion of bile by inhibiting gallbladder contraction
3. Fcn is to conserve digestive enzymes and bile b/w meals
4. CCK stimulates release of pancreatic polypeptide
significance of ATP sensitive K channel and insulin
a. ATP sensitive K channel is a complex of SUR1 and inward rectifying K channel subunits (Kir6.2)
i. Regulators in insulin release
ii. Katp modules the influx of Ca thru VG Ca channels
1. In a normal resting state, Katp is open and VG Ca channels are closedno insulin secreted
2. When glucose is taken up by C cells by GLUT2, the Katp closes utilizing ATP from glucose metabolism and K+ accumulates in the cell, Ca channel opens by depolarization, and influx of Ca triggers insulin exocytosis
neonatal diabetes mellitus*
a. Gain of function mutations of SUR1 and Kir 6.2Katp channels to remain open and decreases insulin secretion and leads to neonatal diabetes mellitus
neonatal hyperinsulinemic hypoglycemia
a. Loss of function mutations of SUR1 and Kir 6.2Katp channels remain closed, and cause an unregulated secretion of insulin leading to neonatal hyperinsulinemic hypoglycemia
