Pancreatic Endocrine Hormones

Question 1

delta cells =

Answer 1

somatostatin and gastrin

Question 2

PP cells =

Answer 2

pancreatic polypeptide

Question 3

which is more important…the ratio between insulin and glucago or their absolute concentrations?

Answer 3

ratio

Question 4

insulin structure

Answer 4

2 polypeptide chains A and B

A chain = 21 aa

B chain = 30 aa

connected by 2 disulfide rings

Question 5

insulin gene

Answer 5

3 exons and 2 introns

direct synthesis of preproinsulin

Question 6

preproinsulin –> prosinsulin

Answer 6

cleaving N terminal signal peptide in RER

proinsulsin = A and B chains and C peptide

Question 7

processing of proinsulin

Answer 7

in golgi (99%)…the rest is secreted

folds so A and B chains can link with disulfide bonds

remove C peptide and package into secretory granules

Question 8

glucose transporter on beta cells

Answer 8

GLUT2

always expressed

Question 9

glucokinase

Answer 9

phosphorylation of glucose in cytoplasm of beta cells

rate limiting step

Question 10

oxidation of glucose –> how does it result in insulin release from beta cells?

Answer 10

ATP build up –> ATP-sensitive K+ channel closes –> K+ efflux is inhibited –> depolarization

–> VG Ca2+ channels open and influx of Ca2+ –> insulin release

Question 11

relationship between plasma insulin and plasma glucose (graph)

Answer 11

sigmoidal

no insulin when below 50mg/dL

half max at 150

max insulin response = 300

Question 12

property of insulin secretion

Answer 12

biphasic to a continuous glucose stimulus

within seconds of glucose exposure…immediate pulse of insulin that peaks at 1min and then returns to base

after 10min…second phase of secretion…which insulin increases more slowly then plateaus for many hours in normal people

Question 13

which amino acids stimulate insulin secretion

Answer 13

Lys

Arg

Question 14

prolonged exercise on insulin levels

Answer 14

decrease

Question 15

circulation of insulin

Answer 15

unbound to any carrier protein

Question 16

most important target tissues for insulin

Answer 16

adipose, liver, muscle

Question 17

insulin receptor

Answer 17

2 alpha and 2 beta subunits

beta = transmembrane
alpha = EC domains...alpha subunits are the ones that are connected (disulfide)

tyrosine kinase receptor***

Question 18

steps once insulin comes in contact with its receptor?

Answer 18

1. activate tyrosine kinase activity in beta subunit
2. auto-phosphorylates the beta subunit
3. phosphorylates tyrosine residues on insulin receptor substrates (IRS)
   - IRS-1 and 2 = muscle, adipose, and liver
   - IRS-3 = brain
4. IRS serve as docking and activating sites for other enzymes
5. specifically PI-3 kinase –> creates PI-3 phosphates
6. glucose transporters (GLUT4) are translocated to membrane….via action of Akt (called PKB or PKC too)

Question 19

which key enzyme in adipose is inhibited by insulin

Answer 19

hormone sensitive lipase

Question 20

glucagon structure

Answer 20

29 aa

residues 1-6 at amino terminus end are important biologically

Question 21

precursor molecule for glucagon

Answer 21

preproglucagon

Question 22

glucose and insulin effects on glucagon transcription

Answer 22

decrease

Question 23

stress on glucagon release

Answer 23

increase synthesis and secretion

Question 24

glucagon receptor

Answer 24

7 transmembrane G protein coupled receptor

acts through stimulatory G proteins (Gs) and therefore functions by increasing cAMP levels

Question 25

in a normal state, insulin:glucagon a few hours a meal

Answer 25

2.0

Question 26

in a fasted state or after prolonged exercise

insulin:glucagon

Answer 26

0.5 or less

Question 27

effect of a high protein meal

Answer 27

increase both insulin and glucagon

insulin inceases uptake of amino acids into muscle and inhibits proteolysis

glucagon inhibits effects of insulin by increasing hepatic glucose output and decrease tissue glucose uptake…thus preventing hypogylcemia

Question 28

regulation of synthesis of somatostain from delta cells

Answer 28

glucose, amino acids, fFAs, glucagons, various GI hormones

inhibited by insulin

Question 29

somatostatin (-) secretion of what hormones

Answer 29

insulin and glucagon

and inhibits uptake of all nutrients from GI tract through inhibition of motility and secretion of most other GI hormones