Signaltransduction of Insulin

Question 1

Diabetes mellitus

Answer 1

hyperglycemia
long term complications
relative /absolute insulin deficiency
Type 1: destruction of B cells
Type 2: insulin resistance, relative insulin deficiency

Question 2

Insulin receptor

Answer 2

transmembrane glycoprotein
2a and 2b - heterotetramer
b subunits can transphosphorylate- activation of tyrosine kinase
Ser/Thr phosphorylation decreases tyrosine kinase activity
activated receptor phosphorylates IRS
can be bound to RTK- docking place for SH2 domains

Question 3

Types of IRS

Answer 3

IRS1,IRS2: ubiquitously expressed
IRS3: adipose tissue
IRS4: kidney, brain

Question 4

Effects of insulin

Answer 4

+ glucose uptake (Glut 4) by muscle
- glucose release from liver glycogen
+ uptake, storage of FA by adipose tissue (Glut4)
- breakdown of fat + release of FAs from adipocytes
+ restitin, leptin, adiponectin secretion from adipocytes

Question 5

Effect of Insulin on organs

Answer 5

Muscle:
-uptake of glucose + storage
Liver:
-uptake of glucose + storage
-glycogen phosphorylase
\+ glycogen synthase
- glucose synthesis
\+ excess glucose -> FA
Adipose tissue:
-glucose uptake -> glycerol -> FA

Question 6

Insulin and Protein metabolism

Answer 6

+ transport of AAs, protein synthesis, gene transcription

- protein degradation, glucose synthesis

Question 7

Insulin and Fat metabolism

Answer 7

Liver:
-glucose -> fat
-TaG synthesis
Adipose:
- TAG degradation
\+ glucose uptake -> glycerol
\+ FA uptake -> TAG

Question 8

Adiponectin

Answer 8

30kDa
made in adipocytes
plasma levels high in normal, low in obese/diabetic
+ endothelial vasodilation, nitric oxide, angiogenesis, insulin sensitivity
- VCAM1, TNFa level, pro inflammatory effect, oxidized LDL, endothelial cell proliferation, growth factor effects on SMC, neointimal thickening, SMC proliferation

Question 9

Insulin resistance

Answer 9

leptin, TNFa, adiponectin, IL-6, resistin contribute
levels low in normals, elevated in obese/diabetic
resistin inhibits glucose uptake, made in white fat

Question 10

Mitogenic effects of insulin

Answer 10

SH2 adaptor proteins

MAP kinase cascade