Postprandial Glucose Metabolism - Pancreatic Function Flashcards
(47 cards)
What is the endocrine role of the pancreas?
1-2% of weight in Islets of Langerhans; production and secretion of insulin, amylin, glucagon, somatostatin, and pancreatic polypeptide
What is the exocrine function of the pancreas?
98-99%; production and secretion of bicarbonate, amylase, trypsin, chymotrypsin, and carboxypeptidase for digestion
What is the structure of the pancreatic islets?
50-500um diameter sphere of 50-300 cells of 4 types: alpha, beta, delta, and theta; beta cells are 80% of the population and comprise the core; the other 3 comprise the outside
Beta cells secrete
(80%) insulin and amylin
Alpha cells secrete
(10%) glucagon
Delta cells secrete
(<5%) somatostatin
Theta cells secrete
(<5%) pancreatic polypeptide
Insulin is synthesized as a
preprohormone
Insulin is cleaved by
PC2 (pre) and PC1 (pro)
The cleaved segment of insulin gene is
C-peptide (connecting peptide)
Insulin forms from
disulphide bonds between the alpha and beta chains of the insulin gene with C-peptide cleaved from between them
Insulin is packaged into
secratory granules containing endopeptidase enzymes
Secretion of insulin is stimulated by
nutrients eg glucose
What are the 2 phases of insulin secretion?
sharp rise (2-5mins) of surface quick-released vesicles; prolonged secretion (for duration of stimulus)
How is the insulin release profile altered in type 2 diabetes?
1st/rapid phase of insulin secretion disappears
Which GLUT receptor takes up glucose into beta cells?
GLUT2
What is unique about GLUT2 and glucokinase?
They both have high Kms; they increase in proportion to the concentration of sugar present
How are beta cells signalled to secrete insulin?
Glucose enters cell via GLUT2; phosphorylated to G6P by glucokinase; enters glycolysis & TCA; increases ATP/ADP ratio which closes a K+ channel; causes depolarization of the membrane and opening of a Ca2+ channel; Ca2+ influx signals vesicle release
GLUT2 and glucokinase are only expressed in
beta cells and liver
How do amino acids trigger insulin secretion by beta cells?
taken up by specific AA transporters; enter TCA as does G6P to increase ADP/ATP ratio, triggering membrane depolarization, Ca2+ influx, and vesicle release (like glucose does)
How do fatty acids trigger insulin secretion by beta cells?
burning of FAs results in an increase in malonyl-CoA which inhibits entry of fats into mitochondria via the carnatine transporter for beta-oxidation; somehow this causes insulin secretion; also a FA receptor FFA1R
more insulin is secreted when glucose is administered _______ than when administered ________
orally; intravenously - this phenomenon is called the incretin effect and is explained by the presence of incretin hormones from the gut causing insulin secretion
What are incretins?
gut derived hormones that are secreted in response to nutrients (glucose, FAs, AAs) that increase insulin production
What are the incretins?
glucagon-like peptide 1 (GLP-1) and glucose-induced insulinotropic polypeptide (GIP)
