Insulin, glucagon, GLP1, CRH

Question 1

Cell types of the pancreas:
B cells secrete?
a cells secrete?
delta?
PP?

Answer 1

B: insulin
- arranged around central core

a-cells: secrete glucagon

Delta: somatostatin

PP:
pancreatic polypeptide

Question 2

What is exposed to higher levels of insulin and glucagon?

Liver, muscle, or adipose?

Answer 2

Liver

- secretion products of the pancreatic cells goes into the portal vein and into the liver first

Question 3

Where are C peptides cleaved when insulin is being synthesized/processed? Why is this significant?

Answer 3

C-pep is cleaved in the secretory vesicles after it leaves the golgi

It is secreted into the blood stream along with insulin

Question 4

Biphasic response of insulin secretion

Answer 4

first phase:
secretion of vesicles of insulin already docked at pm

second phase:
recruitment of cytoplasmic vesicles to the docked position
- will surge if islet cells are responding to high glucose [ ] for 20 min or longer

Question 5

Initiators of insulin release

Answer 5

deez guys stim insulin release on their own!

glucose
aa
drugs - sulfonylureas

Question 6

Potentiators

Answer 6

stim insulin secretion only in presence of glucose
(potentiate glucose effect on insulin)

glucagon
incretin (GLP-1)
acetylcholine

Question 7

Inhibitors of insulin secretion

Answer 7

diazoxide
somatostatin
alpha adrenergic agents

• Long term FA exposure
• Long term hyperglycemia
  (glucose toxicity)

Question 8

How does glucose lead to insulin release?

Answer 8

1. Glucose enters beta cell
2. Glucose is metabolized by glucokinase to G6P
3. ATP is eventually made (phosphoglycerate and pyruvate)
4. Closing of ATP regulated potassium channels
5. depolarization –> VGCC activation + exocytosis of insulin

Question 9

Somatostatin effect on insulin release

Answer 9

somatostatin is made by delta cells, and decreases insulin release

(just like catecholamines and splanchnic n does)

Question 10

Stimulation of the splanchnic nerves does what to insulin secretion?

Answer 10

Inhibits insulin secretion

just like catecholamines and somatostatin does

Question 11

Stimulation of the vagal n with release of ACh has what effect on insulin?

Answer 11

Increase insulin secretion

- This increases insulin with the sight or first taste of food “cephalic phase” of insulin release

Question 12

Which type of diabetes has both insulin resistance and insulin deficiency?

Answer 12

T2D

• early in the course, insulin deficiency is ‘relative’
• insulin lvls are high but not high enough to lower blood glucose levels
• later in the course, insulin lvls are lower than normal

Question 13

Glucose uptake into cells are stimulated by insulin in all but where?

Answer 13

Skeletal m, adipose

not in liver, or brain

Question 14

How does insulin signaling occur ? What effect does it have on the insulin receptor?

Answer 14

The insulin receptor = EGF family, heterotetramer

1. signaling occurs with autophosphorylation of the receptor and other substrates (aa, tyr residues).
2. The P of insulin receptor substrates (IRS) forms the main links for signal transduction btwn rcptr and downstream effector pathways
3. IRS = dockin site for SH2 domain proteins
4. Results in metabolic or mitogenic effects

Question 15

Example of Metabolic pathway activation of insulin release

Answer 15

after auto P and P/activation of IRS –>
stimulates PI3K –>
rapid translocation of GLUT4 into insulin sensitive PM (skeletal/adipose) –>
stim glucose uptake

Question 16

Mitogenic pathway key intermediate

Answer 16

Insulin Receptor Substrates (IRS) –> Map KINASE

not PI3K like in metabolic

Question 17

How can glucagon secretion be inappropriately high in T1D and T2D?

Answer 17

T1D - insulin is low

T2D - insulin resistance

Question 18

GLP-1 analogues help control hyperglycemia how?

Answer 18

reduce glucagon levels

it imitates GLP-1 which it ups insulin response by 50-70% + release

Question 19

Incretin is responsible for how much of the insulin response to oral glucose ingestion

Answer 19

50-70%

Question 20

GLP1 actions

Answer 20

1. Increase insulin secretion when glucose is high only
2. inhibits glucagon secretion
3. inhibits GI secretion and motility
4. inhibits appetite and food intake

Question 21

Will GLP-1 result in weight gain or loss?

Answer 21

Loss - it reduces appetite and does not cause hypoglycemia

Question 22

How are catecholamines different from glucagon in increasing blood glucose?

Answer 22

They affect similar cAMP pathways, but also:

• inhibit insulin secretion
• produce insulin resistance in skeletal m by stim glycogenolysis
• super helpful with hypoglycemia

Question 23

Catecholamines are elevated during?

Answer 23

DKA
stress
surgical stress
trauma

Question 24

Is cortisol response fast or slow?

Answer 24

slow - MOA requires protein synthesis

It is secreted in response to virtually all stressful stimuli

Question 25

Actions of cortisol (3)

Answer 25

1. increase supply of aa available as subtrates but promoting breakdown in m
2. inhibits insulin action
3. potentiates actions of glucagon and catecholamines

Question 26

Chronic use of which can lead to diabetes?
Glucagon,
Catecholamines,
Cortisol

Answer 26

Cortisol/corticosteroids -

its anti insulin effects

Question 27

How does GH (one of the 4 CRH) reduce hypoglycemia?

Answer 27

promotes lipolysis and stim of protein synth
- promote utiliz of proteins

antiinsulin effect
- insulin R can be seen in adolescents with growth spurt or GH tumors