BC 24 Insulin and Glucagon

Question 1

Healthy individual have narrow glucose range

Answer 1

normal : 70-110 mg/dL 3.9-6.1 mmol/L

need to maintain a minimum for brain function and other necessary organs

Question 2

Insulin and Glucagon

Answer 2

pancreatic hormones acting antagonistically to eachother

always a basal level of both

I/G ratio is a more appropriate representation

proteins, synthesized as larger preprohormones

• cleaved to yield prohormones
• cleaved to yield active enzymes

Question 3

Fasting and Fed

Answer 3

Fasting: high insulin/glucagon ratio

Fed: low insulin/glucagon ratio
-or diabetic

Question 4

pancreas

Answer 4

Exocrine: acinar cells involved in secretion of digestive enzymes to duodenum

Endocrine: islets of Langerhans, 1-2% of secretion
-alpha cells: glucagon synthesis and secretion (15-20%)
-B cells: insulin synthesis and secretion (most prominent) and middle
Delta Cells>: somatostatin synth and sec
PP cells: polypeptide synth and secretion

Question 5

insulin biosynthesis

Answer 5

synthesized as inactive precursor (110 AA)

mature is only 51 AA, two polypeptide chains

PTM are involved in pre pro to pro to enz

1. expression in nucleus
2. translation in cytosol
3. signal sequence directs to lumen of ER (hydrophobic). Preproinsulin
4. RER preproin cleaved to release proinsuline. DiS bonds between PP aligned
5. properly folded transported from RER to cis Golgi, cleaved into C peptide and insulin
6. both stored in secretory vesicles
7. at appropriate signal, equal amounts released

high concentration in sec granuals, forms dimers, Zn 2+ hexamers and insulin crystals

Question 6

glucagon biosynthesis

Answer 6

alpha endocrine , L cells of SI and brain

similar to insulin, however, tissue specific

Incretins: insulin secretion stimulating agent

• GLP1 glucagone like pp 1
• reason for higher secretion of insulin in oral vs intravenous glucose
• low levels when fasting but secreted from L cells of intestine in presence of glucose
• GLP stimulates insulin secretion and inhibits glucagon release
• GLP1 short half life, cleaved by DPP4 (dipeptylpeptidase 4)

GLP1: lowered in patiest with dype II diabetes
-incretin mimitics are available for treatment of type II diabetics
Byetta (exanatide)

Question 7

secretion of insulin

Answer 7

regulated OR constitutive
-B cell quickly respond to glucose variation

1. Glut 2 insulin independate transporter
2. glucose phosphorylation
3. flucose is metabolized and ATP levels increased
4. elevated ATP inhibits ATP sensitive K+ channel
5. accumulation of K+ in the cytosol results in membrane depol
6. membrane dpol leads to opening of voltage gated Ca cahnnel
7. increase Ca2 mobilizes secretory granules

NOT ATP sensitive K+ channel is a target for sulfonylurea a drug available to type 2 diabetics (look at image)

Question 8

glucagon secretion

Answer 8

similar?

Question 9

why have GLUT 2 regulated in pac b cells why not glut1 or glut3

Answer 9

regulated,

lower affinity for glucose than one or two, ensures that secretion responds proportionally to change in glucose concentrations

Question 10

turnover rate

Answer 10

first pass effect: 50-60% of insulin and glucagon metabolized by the liver via receptor mediated andocytosis

kidneys play a role

short half lives (minutes). insulin 3-5 glucagon 5

c-peptide longer half life can be a reliable reflection of insulin secretion

Question 11

Regulation of insulin

Answer 11

Counter regulatory hormones counteract the action of insulin
-glucagon/epinephrine/cortisol/GH

Insulin
\+blood glucose
\+dietary AA
\+Incretins
-epinephrine
\+/- neural input

Glucagon
-blood glucose
\+dietary AA
-insulin incretins
\+epinephrine
\+neural output
\+cortisol GH

both have AA to deal with high protein low carb diet, small insulin enough to prevent self protein degradation

Question 12

Signal Tarnsduction

Answer 12

Insulin Receptor
RTK
liver/muscle adipose tissue
-binding of insulin, signal trans cascade dephosphorylating the target enzyme

Glucagon receptor
GPCR
liver
binding of glucagon, signal trans cascade, phosphorylation of the enzyme

Question 13

glucose homeostasis

Answer 13

glucose uptake insulin independent in many tissues

glucose uptake is insulin dependent in muscle and adopose, only muscle and adipose produce glut 4

high I/G ratio: glut 4 lowers elevated BG Insulin Inside

low I/G ratio: Glut 4 returns to endocytic vesicles glucose synthesis and section induced

nned GLUT4 here bc they represent the mass of the body, (musle/adipo) and would use all glucose from brain/rbc

Question 14

know when each are on

Answer 14

fed: insulin, move nutrients from blood to storage, increase synthesis of macromolecules, glycogen, FA, proteins
fast: glucagon, mobilize nutrients from storage to blood, breakdown macromolecules (glycogen, FA, proteins) use FA and Ketone bodies as E source (except brain and RBC)

Question 15

look at last three slides

Answer 15

be able to explain them