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Drew 921 > 6_InsulinGlucagon > Flashcards

6_InsulinGlucagon Flashcards

1
Q

Who discovered insulin in 1923?

A

Frederick Banting and John Macleod

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2
Q

Who sequenced insulin in 1958?

A

Fredrick Sanger

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3
Q

Who performed x-ray crystallography of insulin in 1964?

A

Dorothy Hodgkin

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4
Q

Who developed RIA to measure insulin concentration?

A

Rosalyn Yellow

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5
Q

What structures make up the exocrine glands of the pancreas?

A

acini

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6
Q

What structures make up the endocrine glands of the pancreas?

A

islets of langerhans

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7
Q

Function of the alpha cells?

A

secrete glucagon

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8
Q

Function of the delta cells?

A

secrete somatostatin

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9
Q

Function of the beta cells?

A

secrete insulin, C peptide, and amylin

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10
Q

Function of the PP cell?

A

secretes pancreatic polypeptide

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11
Q

What are the pancreatic cells’ relative percentages of abundance of the pancreas?

A

alpha = 25%, beta = 60%, delta = 10%

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12
Q

How is insulin stored?

A

in secretory granules as the hexamer

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13
Q

Describe insulin’s half-life and binding in plasma?

A

unbound, 6 minutes

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14
Q

Describe the structure of insulin.

A

A and B chains linked by 2 di-sulfide bridges; A chain has third disulfide bridge

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15
Q

How many AA’s is insulin, and what is its mass?

A

51 AA, 5.8 kDa

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16
Q

What kind of receptor is the insulin receptor?

A

RATK

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17
Q

What factors cause an increase in insulin secretion?

A

1) glucose, 2) glucagon, 3) GH, 4) cortisol, 5) FFAs, 6) Arg/Lys, 7) GI hormones, 8) PNS, 9) beta-adrenergic stimulation, 10) insulin resistance/obesity

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18
Q

What are the mechanisms of the sulfonylureas?

A

ATP-gated K+ channel blockers prevent depolarization of the beta cell

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19
Q

What factors cause a decrease in insulin secretion?

A

decrease in glucose, fasting, somatostatin, alpha-adrenergic stimulation, leptin

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20
Q

Describe the events leading up to insulin secretion.

A

1) GLUT2 imports glucose causing increase in ATP, 2) ATP closes ATP-gated K channel causing depolarization, 3) Ca channels are activated 4) Ca stimulates vesicle-plasmalemma fusion causing exocytosis

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21
Q

How many phases in insulin secretion?

A

Phase I and Phase II

22
Q

Describe Phase I of insulin release.

A

initial release of stored insulin within 3-5 minutes

23
Q

Describe Phase II of insulin release.

A

release of additional stored insulin and new synthesis at 15 minutes; peaks at 2-3 hours

24
Q

What is proinsulin?

A

A, B, and C peptides of insulin still joined

25
When is proinsulin cleaved?
in the secretory granule
26
What is the initial translation product of the insulin mRNA?
pre-proinsulin
27
Describe the structure of the insulin RATK.
2 extracellular alpha chains disufide-bonded to 2 membrane-spanning beta chains
28
Describe the receptor pathway for the InsRATK
glucose binds the alpha subunits; beta subunits are auto-phosphorylated; local TK activated
29
When do muscle cells become more permeable to glucose for glucose utilization?
with insulin secretion and during contraction
30
What is the normal energy source of muscle cells?
fatty acids; only slightly permeable to glucose without insulin
31
What is the function of the SREBP-1c gene?
produces a transcription for an increase in FA synthesis enzymes
32
Where kind of glucose receptors does the liver have?
GLUT-1
33
How does GLUT-1 respond to insulin?
it doesn't
34
What are insulin's effects in the liver?
1) increased FA synthesis from glucose if glycogen at its 5-6% capacity via upregulation of SREBP-1c; 2) increase uptake & storage of glucose by activating glycogen synthesis enzymes; 3) decreases glycogenolysis by inactivating liver phosphorylase and glucose phosphatase; 4) decreases gluconeogenesis
35
What causes gluconeogenesis and glucose release from the liver under fasting conditions?
lack of insulin (just takes off the brakes)
36
What is the rate-limiting step in FA synthesis?
acetyl-CoA-carboxylase (acetyl-CoA to malonyl-CoA)
37
What are insulin's effects in adipocytes?
1) primarily inhibits hormone-sensitive lipase to decrease stored TG hydrolysis; 2) promotes GLUT4 translocation for TG synthesis; 3) increases FA synthesis; 4) increases G3P synthesis
38
How are FFAs created in adipose tissue?
from FFA's in blood, from stored TG hydrolysis, and from de novo synthesis
39
What are insulin's effects of protein metabolism?
1) increased anabolism, 2) decreased gluconeogenesis, 3) increased AA uptake (synergistic with GH)
40
What are insulin's effects in the brain?
none; insulin not required for glucose uptake
41
What happens in insulin lack?
HPL activated to increase FFA's; ketone bodies increase
42
What are the effects of somatostatin?
extends time for nutrient absorption: 1) decreases insulin, 2) decreases glucagon, 3) decreases GI motility, 4) decreases GI secretions and absorption
43
What is the half-life of somatostatin?
3 minutes
44
How is glucagon synthesized?
as a pre-prohormone
45
Describe glucanon's binding and half-life.
short half-life, unbound
46
What is glucagon's receptor pathway?
1) primary is G-alpha-S to activate PKA; 2) minor pathway is G-alpha-q; 3) also decreases glycogen synthase
47
What are PKA's effects when stimulated by glucagon?
1) glycogenolysis (activates GPK); 2) gluconeogenesis (activates PGC1, PEPCK, G6P)
48
What enzymes does glucagon activate?
G6Pase, GPK
49
What enzymes does glucagon inhibit?
Glycogen synthase
50
How is glucagon secretion stimulated?
1) hypoglycemia, 2) exercise, 3) increased Ala/Arg
51
Why do increased Ala and Arg stimulate glucagon release?
glucagon facilitates AA conversion to glucose
52
What effect do increased Ala/Arg have on insulin secretion?
stimulate! Same as glucagon.

Drew 921 (33 decks)

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