chapter 9 - endocrine pancreas Flashcards

1
Q

what does pancreas secrete

A

insulin, glucagon, - regulate glucose, FA and AA metabolism

also somatostatin and pancreatic polypeptide

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2
Q

islets of langerhans

A

have 4 cell types:
beta - insulin
alpha - glucagon
delta - somatostatin
others secrete pancreatic polypeptide or other peptides
central core mostly beta, alpha around rim, delta interspersed between alpha and beta

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3
Q

ways cells of islet of langerhans communicate with each other (3)

A

1: gap junctions connect A to each other, B to each other, and A to B
2: recieve about 10% of total pancreatic blood flow - venous blood from one cell type bathes other cell types
3: innervated by adrenergic, cholinergic and peptidergic neurons

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4
Q

insulin

A

synthesized and secreted by beta cells
2 straight chains (A and B)
A linked to B by 2 disulfide bridges
A has third bridge

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5
Q

chromosome 11

A

location of gene that directs synthesis of insulin

member of superfamily of genes that encode related growth factors

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6
Q

proinsulin

A

made very early in biosynthetic process
shuttled to ER where disulfide bridges form
packaged into secretory granules on golgi - proteases cleave to make insulin

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7
Q

connecting peptide

A

part of proinsulin that is cleaved off
packaged with the insulin in the secretory granule
released in equilmolar quantities with insulin
basis for a test for beta-cell function in persons with type I diabetes mellitus

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8
Q

degradation of insulin

A

metabolized in liver and kidney by enzymes that break disulfide bonds
a and B chains released and excreted in urine

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9
Q

mechanism of insulin secretion

A

1: transport of glucose into the beta cell via Glut2 (via facilitated diffusion)
2: glucose phosphorylated to glucose-6-phosphate by glucokinase
3: glucose-6-phosphate is oxidized - generates ATP
4: ATP causes K+ channels in B-cell membrane to close
5: cell depolarized
6: depolarization opens V-G Ca2+ channels in membrane
7: Ca2+ flows into cell down electrochemical gradient
8: increased intracellular Ca2+ causees exocytosis of insulin-containing secretory granules
9: insulin secreted into pancreatic blood and delivered to systemic circulation - C peptide secreted in equilmolar amounts

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10
Q

stimulatory factors for insulin secretion

A
increased glucose concentration
increased AA concentration
increased FA and ketoacid concentration
glucagon
cortisol
glucose-dependent insulinotropic peptide (GIP)
potassium
vagal stimulation; ACTH
sulfonyleura drugs (eg tolbutamide, glyburide)
obesity
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11
Q

inhibitory factors for insulin secretion

A
decreased blood glucose
fasting
exercise
somatostatin
alpha-adrenergic agonists
diazoside
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12
Q

glucose dependent insulinotropic peptide (GIP)

A

secreted in response to oral glucose
GI hormone that has an independent stimulatory effect on insulin secretion (adding to the direct effect of glucose on beta cells)
IV glucose doesn’t have this indirect effect so doesn’t stimulate insulin secretion as much as oral glucose does

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13
Q

glucagon

A

activates a Gq portein coupled to phospholipase C => rise in intracellular Ca2+ => exocytosis of insulin

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14
Q

somatostatin

A

inhibits mechanism that glucagon stimulates

Gq protein coupled to phospholipase C => ris in intracelllular Ca2+/IP3

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15
Q

sulfonylurea drugs

A

used to treat type II (non-insulin dependent) diabetes mellitus
stimulate insulin release from beta cells by closing the ATP-dependent K+ channels, depolarizing cell, and mimicking the depolarization induced by glucose

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16
Q

insulin receptor structure

A

insulin receptor is a tetramer with two alpha and two beta subunits
alpha = extracellular
beta = across cell membrane
disulfide bond connects two alpha, each alpha connected to a beta by a disulfide bond
beta have tyrosine kinase activity

17
Q

mechanism of action of insulin

A

1: insulin binds to alpha subunits => conformational change
2: activates tyrosine kinase in beta subunit
3: autophosphorylation with ATP
4: activated tyrosine kinase activates other enzymes/proteins
5: insulin-receptor complex is internalized by endocytosis
6: insulin receptor degraded, stored, or recycled
7: insulin down-regulates its receptor by decreasing rate of synthesis and increasing rate of degradation
8: insulin binds to elements in the nucleus, golgi, and ER
9: stimulates gene transcription

18
Q

insulins actions on blood glucose concentration

A

hypoglycemic action
causes both decrease in blood glucose concentration and limits rise in blood glucose that occurs after eating carbs
does so by:
1: increases glucose transport into target cells such as muscle and adipose by directing the insertion of glut4 transporters => insulin enters cells and blood glucose level decreases
2: promotes formation of glycogen from glucose in liver and in muscle
3: inhibits glycogenolysis
4: inhibits gluconeogenesis by increasing production of fructose 2,6-biphosphate => increased phosphofructokinase activity - directs substates away from formation of glucose

19
Q

actions of insulin on FA and ketoacid concentrations

A

inhibits mobilization and oxidation of fatty acids
increases storage of FA
overall decreases circulation levels of FA and ketoacids
in adipose: stimulates fat deposition
inhibits lipolysis
in liver: inhibits ketoacid formation

20
Q

insulin effect on blood AA concentration

A
overall anabolic
increases AA and protein uptake by tissues
=> decreased blood levels of AA
increases protein synthesis 
inhibits protein degradation
21
Q

insulin actions on K+ levels

A

increases activity of Na/K-ATPase => increased K+ uptake into cells
protects against increased K+ due to dietary uptake

22
Q

hypothalamic satiety center

A

insulin appears to have direct effect

23
Q

actions of insulin (list)

A

1: increases glucose uptake into cells => decreased blood glucose
2: increases glycogen formation
3: decreases glycogenolysis
4: increases protein synthesis => decreases blood AA
5: increases fat deposition => decreased blood FA
6: decreases lipolysis => decreased blood ketoacid
7: increases K+ uptake into cells => decreased blood K+

24
Q

insulin-dependent diabetes mellitus (type I diabetes)

A

caused by destruction of beta cells
often result of an autoimmune process
beta cells dont’ secrete adequate insulin => carbohydrate, fat and protein metabolism disturbed
=>
1: increased blood glucose concentration from decreased uptake into cells, decreased glucose utilization, increased gluconeogenesis
2: increased blood FA and ketoacid concentrations due to increased lipolysis of fat, increased conversion of FA to ketoacids, and decreased utilization of ketoacids by tissues
3: increased blood AA concentrations due to increased breakdown of protein to AA
4: loss of lean body mass and loss of adipose tissue
5: diabetic ketoacidosis due to increased levels of ketoacids
6: osmotic diuresis, polyuria and thirst due to large amounts of nonreaborbed glucose in urine
polyuria => ECFV contraction and hypotension
7: shift of K+ out of cells => hyperkalemia
treatment = insulin replacement therapy

25
Q

diabetic ketoacidosis (DKA)

A

metabolic acidosis due to increased levels of ketoacids in diabetes type I patients

26
Q

non-insulin dependent diabetes mellitus (type II diabetes)

A

often associated with obesity
cuased by down-regulation of insulin receptors in target tissues and insulin resistance
insulin secreted normally, but at normal concentrations it can’t activate its receptors on muscle, liver, and adipose tissue
blood glucose concentration elevated in both fasting and postprandial states
treate with caloric restriction adn weight reduction, sulfonylurea drugs, which stimulate pancreatic insulin secretion, and with biguanide drugs (metformin) which up-regulated insulin receptors on target tissue

27
Q

glucagon

A

synthesized by alpha cells on islets of langerhans

promotes mobilization and utilization of metabolic fuels

28
Q

structure of glucagon

A

single, straight polypetide, 29 AA

member of family of peptides that includes secretin and gastric inhibitory peptide (GIP)

29
Q

stimulatory factors of glucagon secretion

A
fasting
decreased glucose concentration
increased AA concentration, especially arginine
cholecystokinin (CCK)
beta-adrenergic agonists
acetylcholine
30
Q

inhibitory factors of glucagon secretion

A

insulin
somatostatin
increased FA and ketoacid concentration

31
Q

cholecystokinin

A

stimulates glucagon secretion

secreted from GI tract when protein or fat is ingested, and during fasting and intense exercise

32
Q

mechanism of action of glucagon

A

hormone binds to receptor coupled with adenylyl cyclase via Gs protein
second messenger is cAMP
activates protein kinases

33
Q

glucagon on blood glucose concentrationd

A

increases blood glucose concentration by:

1: stimulating glycogenolysis
2: inhibits glycogen formation
3: increases gluconeogenesis by decreasing production of fructose 2,6-bisphosphate => decreased phosphofructoknase activity

34
Q

glucagon on blood fatty acid and ketoacid concentration

A

increases lipolysis and inhibits FA syntehsis
also shunts substrates toward gluconeogenesis
ketoacids produced from FA

35
Q

actions of glucagon (list)

A

1: increases glycogenolysis => increased blood glucose
2: increases gluconeogenesis
3: increases lipolysis => increased blood FA
4: increases ketoacid formation => increased blood ketoacid

36
Q

somatostatin structure and production

A

14 AA
secreted by delta cells
GI counterpart has 28 AA
stimulated by ingestion of all forms of nutrients, several GI hormones, and by B-adrenergic agoinsts
inhibited by insulin via intraislet paracrine mechanism

37
Q

actions of somatostatin

A

inhibits secretion of insulin and glucagon via paracrine actions on alpha and beta cells
modulates or limits the responses of insulin and glucagon to ingestion of food