chapter 9 - endocrine pancreas

Question 1

what does pancreas secrete

Answer 1

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

also somatostatin and pancreatic polypeptide

Question 2

islets of langerhans

Answer 2

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

Question 3

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

Answer 3

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

Question 4

insulin

Answer 4

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

Question 5

chromosome 11

Answer 5

location of gene that directs synthesis of insulin

member of superfamily of genes that encode related growth factors

Question 6

proinsulin

Answer 6

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

Question 7

connecting peptide

Answer 7

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

Question 8

degradation of insulin

Answer 8

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

Question 9

mechanism of insulin secretion

Answer 9

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

Question 10

stimulatory factors for insulin secretion

Answer 10

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

Question 11

inhibitory factors for insulin secretion

Answer 11

decreased blood glucose
fasting
exercise
somatostatin
alpha-adrenergic agonists
diazoside

Question 12

glucose dependent insulinotropic peptide (GIP)

Answer 12

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

Question 13

glucagon

Answer 13

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

Question 14

somatostatin

Answer 14

inhibits mechanism that glucagon stimulates

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

Question 15

sulfonylurea drugs

Answer 15

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

Question 16

insulin receptor structure

Answer 16

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

Question 17

mechanism of action of insulin

Answer 17

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

Question 18

insulins actions on blood glucose concentration

Answer 18

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

Question 19

actions of insulin on FA and ketoacid concentrations

Answer 19

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

Question 20

insulin effect on blood AA concentration

Answer 20

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

Question 21

insulin actions on K+ levels

Answer 21

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

Question 22

hypothalamic satiety center

Answer 22

insulin appears to have direct effect

Question 23

actions of insulin (list)

Answer 23

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+

Question 24

insulin-dependent diabetes mellitus (type I diabetes)

Answer 24

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

Question 25

diabetic ketoacidosis (DKA)

Answer 25

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

Question 26

non-insulin dependent diabetes mellitus (type II diabetes)

Answer 26

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

Question 27

glucagon

Answer 27

synthesized by alpha cells on islets of langerhans

promotes mobilization and utilization of metabolic fuels

Question 28

structure of glucagon

Answer 28

single, straight polypetide, 29 AA

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

Question 29

stimulatory factors of glucagon secretion

Answer 29

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

Question 30

inhibitory factors of glucagon secretion

Answer 30

insulin
somatostatin
increased FA and ketoacid concentration

Question 31

cholecystokinin

Answer 31

stimulates glucagon secretion

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

Question 32

mechanism of action of glucagon

Answer 32

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

Question 33

glucagon on blood glucose concentrationd

Answer 33

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

Question 34

glucagon on blood fatty acid and ketoacid concentration

Answer 34

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

Question 35

actions of glucagon (list)

Answer 35

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

Question 36

somatostatin structure and production

Answer 36

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

Question 37

actions of somatostatin

Answer 37

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