Pancreatic Hormones I

Question 1

What are islets of Langerhans?

Answer 1

Discrete clusters of endocrine cells in the pancreas

B cells - secrete insulin

a cells - secrete glucagon

Also contain cells that secrete somatostatin and pancreatic polypeptide

Question 2

How is insulin made and degraded?

Answer 2

Synthesized and packaged as proinsulin, the secretory granules contain prohormone-converting enzymes that cleave proinsulin into insulin and C peptide

Liver is the principal site of insulin degradation, half life of 5-8 minutes

Question 3

What is the daily pattern of insulin production?

Answer 3

Low basal level of production and episodic peaks following food ingestion

Question 4

What substances stimulate insulin production associated with food ingestion?

Answer 4

Glucose - the principal physiological stimulus that evokes insulin release

Amino Acids

Incretins (GIP and GLP-1) - released by intestinal endocrine cells, both glucose dependent

Question 5

What occurs to incretins in T2DM?

Answer 5

Incretin secretion is preserved, but the B cell response to incretins is impaired

Question 6

What is the mechanism of insulin release from B cells?

Answer 6

Glucose diffuses through GLUT2 and is metabolized to G6P

This causes an increase in ATP, which inhibit K efflux through ATP-gated K channels

The decrease in K efflux depolarizes the membrane, and activates Ca channels

The influx of calcium triggers the release of insulin

Question 7

What are sulfonylureas?

Answer 7

Oral hypoglycemic drugs used for treatment of T2DM

Bind to SURe subunit of ATP-gated channels, causing it to close, and therefore causing insulin secretion

Question 8

What are plasma levels of C-peptide used for clinically?

Answer 8

Used to assess insulin secretion by a diabetic patient being treated with exogenous insulin

Question 9

What is the paracrine regulation of the pancreatic islets

Answer 9

Somatostatin inhibits insulin and glucagon release

Glucagon stimulates insulin release

Question 10

How is insulin indirectly controlled?

Answer 10

Hormones indirectly stimulate insulin secretion because their actions antagonize the effects of insulin on glucose homeostasis

E.g. GH and cortisol

Question 11

Describe the neural control of insulin release

Answer 11

Sympathetic stimulation - inhibit release via alpha2 adrenergic receptors

Parasympathetic (vagal) - Promotes insulin release

Question 12

What is the insulin receptor?

Answer 12

Receptor tyrosine kinase, autophosphorylates when insulin binds and phosphorylates other proteins

Question 13

What pathway does the insulin receptor activate?

Answer 13

PI-3 kinase/Akt signal transduction pathway

Question 14

What is the fate of the hormone-receptor complex?

Answer 14

Brought in via endocytosis and the receptor is dephosphorylated

The acidic pH of the endosome degrades the insulin, this is the major mechanism for hepatic clearance of insulin

The receptor is either degraded or recycled

Question 15

How does serine phosphorylation affect the signal intensity of insulin?

Answer 15

Decreases it

Serine phosphorylation on either the receptor or IRS

Question 16

What is the effect of chronic insulin exposure on insulin receptors?

Answer 16

Chronic exposure to elevated insulin levels promotes the down-regulation of insulin receptors

Obesity or periods of high carb intake

Question 17

What are the principal targets of insulin?

Answer 17

Liver

Skeletal muscle

Adipose tissue

Question 18

How is glucagon synthesized?

Answer 18

Derived from perproglucagon which can produce several products

Pancreatic a cell - produces glucagon

Intestinal L cell - produces GLP-1

Question 19

What is the most important physiological stimulus for glucagon?

Answer 19

Hypoglycemia

High protein, low carbohydrate meals also stimulate glucagon due to a cell responsiveness to amino acids

Question 20

What is the affect of sympathetic stimulation on glucagon?

Answer 20

Mediates the response to hypoglycemia via B2 adrenergic receptors

Question 21

What inhibits glucagon release?

Answer 21

Insulin and somatostatin

Question 22

What is the effect of exercise and stress on glucagon release?

Answer 22

Promotes glucagon release

Question 23

What is the primary target and action of glucagon?

Answer 23

Liver

Stimulates hepatic glycogenolysis

Causes the phosphorylation of inhibitor 1, which decreases the conversion of phosphrylase a to Phos. b

(Maintains glycogenolysis)

Stimulates gluconeogenesis

Question 24

What is the absorptive state?

Answer 24

Period of time during and after the ingestion of a meal when cell metabolism is fueled primarily by the nutrients absorbed from that meal

Question 25

What occurs to the insulin-glucagon ratio when a person ingests a balanced meal or a meal that is high in carbohydrates?

Answer 25

Insulin-glucagon ratio increases because the absorbed nutrients have a net stimulatory effect on insulin release and net inhibitory effect on glucagon release

Question 26

What is the GLUT2 transporter?

Answer 26

Transports glucose across the plasma membrane of liver cells by F.D.

Bidirectional transporter with a low affinity for glucose, allows transport into the liver during the absorptive state when glucose is high

Question 27

When does GLUT2 transport glucose out of the liver?

Answer 27

When hepatic glucose production is stimulated during a fast