Postprandial Glucose Metabolism - Pancreatic Function Flashcards Preview

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Flashcards in Postprandial Glucose Metabolism - Pancreatic Function Deck (47):
1

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

2

What is the exocrine function of the pancreas?

98-99%; production and secretion of bicarbonate, amylase, trypsin, chymotrypsin, and carboxypeptidase for digestion

3

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

4

Beta cells secrete

(80%) insulin and amylin

5

Alpha cells secrete

(10%) glucagon

6

Delta cells secrete

(<5%) somatostatin

7

Theta cells secrete

(<5%) pancreatic polypeptide

8

Insulin is synthesized as a

preprohormone

9

Insulin is cleaved by

PC2 (pre) and PC1 (pro)

10

The cleaved segment of insulin gene is

C-peptide (connecting peptide)

11

Insulin forms from

disulphide bonds between the alpha and beta chains of the insulin gene with C-peptide cleaved from between them

12

Insulin is packaged into

secratory granules containing endopeptidase enzymes

13

Secretion of insulin is stimulated by

nutrients eg glucose

14

What are the 2 phases of insulin secretion?

sharp rise (2-5mins) of surface quick-released vesicles; prolonged secretion (for duration of stimulus)

15

How is the insulin release profile altered in type 2 diabetes?

1st/rapid phase of insulin secretion disappears

16

Which GLUT receptor takes up glucose into beta cells?

GLUT2

17

What is unique about GLUT2 and glucokinase?

They both have high Kms; they increase in proportion to the concentration of sugar present

18

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

19

GLUT2 and glucokinase are only expressed in

beta cells and liver

20

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)

21

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

22

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

23

What are incretins?

gut derived hormones that are secreted in response to nutrients (glucose, FAs, AAs) that increase insulin production

24

What are the incretins?

glucagon-like peptide 1 (GLP-1) and glucose-induced insulinotropic polypeptide (GIP)

25

GIP comes from the

upper small bowel

26

GLP-1 comes from the

lower small bowel

27

GLP-1 is a fragment of the

glucagon gene - processed to different hormones depending on tissue

28

GLP-1 stimulates insulin secretion only when

glucose is high

29

GLP-1 is secreted from

L-cells in small intestine in response to glucose and FA

30

GLP-1 binds to

receptor on beta cells

31

What are the actions of GLP-1?

stimulates insulin release and proinsulin/insulin biosynthesis (only if glucose is low); inhibits gastric emptying; inhibits glucagon secretion; promotes beta cell proliferation, differentiation, and maturation

32

Why can't GLP-1 be used directly in treatment of T2D?

half-life is only 2-3mins

33

What are the incretin-based therapies?

DPP-4 inhibitors - incretin enhancers that inhibit the enzyme that degrades GLP-1; GLP-1R agonists -incretin mimetics eg exenatide

34

What is exenatide?

byetta - GLP-1R agonist in the tx of T2D; causes a drop in HbA1c and some weight loss

35

What is the concern over incretin-based therapies?

DPP-4 inhibitors and GLP-1R agonists may cause increases in pancreatitis and pancreatic cancer

36

GIP is secreted from

K cells of duodenum in response to glucose and FAs

37

What are the actions of GIP?

stimulates insulin release; activates lipoprotein lipase to enhance fat clearance from the blood; its effects are dependent on plasma glucose concentration

38

GIP binds to

a receptor on beta cells

39

Amylin is released from

beta cells

40

What are the actions of amylin?

inhibits glucagon secretion; delays gastric emptying; inhibits food intake

41

In type 1 diabetes, amylin

is deficient because the beta cells are destroyed

42

Glucagon is secreted from

alpha cells in response to low blood glucose

43

What is the action of glucagon?

stimulates liver to release glucose to restore normal blood glucose

44

Pancreatic polypeptide is secreted from

theta cells after a meal

45

What are the actions of pancreatic polypeptide?

inhibits food intake; increases energy expenditure; inhibits secretion of pancreatic enzymes; blocks contraction of gallbladder

46

Somatostatin is released from

delta cells following a mixed meal

47

What are the actions of somatostatin?

inhibits insulin and glucagon secretion; inhibits pancreatic exocrine function; main function to prevent exaggerated hormonal responses to a meal