Energy Homeostasis - The endocrine pancreas

Question 1

Pancreatic islet contains

Answer 1

• alpha cells - glucagon
• beta cells - insulin
• delta cells - somatostatin

Question 2

glucagon increases what

Answer 2

blood glucose

Question 3

insulin decreases what

Answer 3

blood glucose

Question 4

in insulin, they have alpha and beta chains connected by ?

Answer 4

disulfide bonds

Question 5

insulin is degraded by ?

Answer 5

insulinase

Question 6

what is released alongside insulin and can be used to determine how much endogenous insulin is secreted

Answer 6

C-peptide

Question 7

what is the pathway for insulin secretion

Answer 7

low glucose -> increased ADP:ATP ration -> open K+ channels -> hyperpolarization -> depolarization -> VGC opening -> Exocytosis of insulin

Question 8

what happens when insulin binds to its receptor

Answer 8

insulin binds to its receptor -> dimerization -> activating protein tyrosine kinase activity

Question 9

what are the key pathways from insulin receptor activation

Answer 9

• PI3K pathway -> Akt and mTOR activation
• IRS activates Ras -> Raf activation -> MEK & MAPK activation -> protein synthesis

Question 10

cells that are chronically exposed to high levels of insulin:

Answer 10

• reduce the number of insulin receptors expressed
• down-regulate some signaling pathways distal to receptor activation

Question 11

what are the stimulators of insulin secretion

Answer 11

• Nutrients in the bloodstream
  ○ Glucose (major)
  ○ Amino acids (arg, lys)
  ○ Free fatty acids
• Hormonal signals
  ○ CCK, GIP (gastric inhibitory polypeptide), and GLP-1 (glucagon-like peptide) are released from the small intestine in response to food – these are known as incretins
  ○ parasympathetic innervation – mostly from the cephalic phase of digestion
  ○ GH – needed for normal insulin secretion

Question 12

what are the inhibitors for insulin secretion

Answer 12

• Hormones
  ○ Somatostatin
  ○ Epinephrine
  ○ Leptin
• Sympathetic nervous system
  ○ Both epinephrine and norepinephrine can inhibit insulin secretion – mediated by alpha receptors
  ○ Stimulation of beta-receptors can stimulate some insulin secretion – however, activation of the SNS results in net inhibition of insulin secretion

Question 13

what are the insulin-independent glucose transporters?

Answer 13

○ SGLT-1 and SGLT-2: intestine and kidney
○ GLUT-1 and GLUT-3: wide distribution
- GLUT-2: liver and pancreas

Question 14

what is the major insulin dependent glucose transporter?

Answer 14

GLUT-4

Question 15

what are the insulin to liver effects?

Answer 15

1. increased glucose uptake from bloodstream
2. increased glucose use
3. increased fatty acid synthesis and VLDL formation
4. decreased ketogenesis
5. increased protein synthesis and decreased urea cycle activity

Question 16

proglucagon includes?

Answer 16

amino acid sequence that can yield glucagon-related polypeptide (GRPP), glucagon, IP-1, GLP-1, IP-2, and GLP-2

Question 17

what cleaves proglucagon at points that yield GRPP, glucagon, and a C-terminal fragment

Answer 17

proteases

Question 18

what stimulates glucagon synthesis

Answer 18

• drops in blood glucose
• rise in serum amino acids
• cortisol
• sympathetic nervous system stimulation
• exercise, stress

Question 19

what inhibits glucagon synthesis

Answer 19

• rise in blood glucose
• stomatostatin

Question 20

what are the glucagon to liver effects

Answer 20

1. increased glucose “output” to other tissues
2. increased beta oxidation
3. increased ketogenesis
4. increased urea cycle activity

Question 21

when there is a high ration of insulin/glucagon

Answer 21

anabolic state

Question 22

when there is a low ration of insulin/glucagon

Answer 22

catabolic state

Question 23

somatostatin tends to ?

Answer 23

decrease the secretion of both insulin and glucagon