Incretin Hormones.

Question 1

What is the incretin effect?

Answer 1

A significantly enhanced insulin secretory response to oral glucose compared to the same dose administered i.v.

Question 2

What are incretins and give 2 examples.

Answer 2

Sam peptide hormones released from the GI tract following food intake that increases the insulin secretory responmse to glucose by 60%/

GIP - slucose dependant insuiliinotropic polypeptide.

GLP-1 - glucagon like peptide 1.

Question 3

GIP?

Answer 3

42AA, from proGIP in the K cells of the GI tract - increase in response to CHO and fat. Transported to the iselts in the blood where they increase insulin release (when BGL is high).

Question 4

GLP-1?

Answer 4

30AA, from proglucagon in L cells of the Gi tract. Proglucagon is deferentially cleaved to produce glucagon (islets) and GLP-1 and 2 in L cells.

Increase insulin, decrease glucagon, delay gastric emptying, decrease apetie and increase B cell mass.

Question 5

What happens to the incretin effect in type 2 diabetes?

Answer 5

Decreased - reduced insulin secretion in response to oral glucose.

Question 6

How could we treat T2DM bearing in mind the decreased incretin effect?

Answer 6

GIP levels - normal but decreased effect - not an option.
GLP - low levels but what is there does work - therefore replace GLP

BUT short lived effect as DPP4 cleave 2 amino acids to render GLP-1 inactive.

DPP4 inhibitors - increase endogenous GLP-1.

Exenatide - anaolgue of GLP1 - similar structure. Stimulates insulin release in an insulin dependant manner.

Question 7

What do GLP-1 anagloues do?

Answer 7

Destroy B cells - BAD!
Inhibit glucagon seretion = decrease glucose production by the liver - good!! Decrease BGL.

Weight loss!

Give with insulin!

Question 8

Effects of GLP-1 on the brain.

Answer 8

Increase neuroprotection.

Decrease appetite.

Question 9

Effects of GLP-1 on the stomach.

Answer 9

Decrease gastric emptying (slower increase in BGL)

Question 10

Effects of GLP-1 on the pancreas.

Answer 10

Increase insulin biosynthesis.
Increase B cell mass
Decrease B cell apoptosis.
Increase insulin
decrease glucagon

Question 11

Effects of GLP-1 on the muscle.

Answer 11

Increase insulin sensitvity

Question 12

Effects of GLP-1 on the liver

Answer 12

Decrease glucose production

Question 13

Effects of GLP-1 on the heart.

Answer 13

Increase cardiac output.

Increase cardioprotection