Topic 7.4 Flashcards
“type” of molecule that insulin is
antidiabetic / antiketogenic
2 steps of insulin synthesis
- pre-pro-insulin
- pro-insulin
- insulin + c peptide
How is insulin stored?
complexed with Zn2+ in granules (180 units in pancreas)
2 stages of electrical activity of beta cells
- early peak phase
- sustained phase
Difference between EPP and SP?
EPP : the readily releasable pool of granules is released, SP has more granules not near the membrane released
What does glucose induce? (2)
- Exocytosis of insulin
- Transcription of insulin (if long exposure)
What is the incretin effect?
feed forward mechanism that increases insulin secretion
Which molecules contribute to incretin effect?
- GLP and GIP (enterohormones)
What do GLP and GIP bind to?
Gs coupled receptor
Which molecules can decrease glucagon secretion?
GLP-1
7 activators of insulin secretion
- Glucose
- AA (K, R, L)
- Enterohormones (GLP, GIP)
- Glucagon
- B adrenergic R
6 Vagus stimulation via M1R - FFA
4 inactivators of insulin secretion
- Hypoglycaemia
- SST
- Leptin
- Alpha2R
(Gi receptors)
Where can we find K-ATP
- beta cells of pancreas
- in SA node
- in vascular smooth muscle
What is K-ATP?
ATP regulated K+ channel
7 steps of release of insulin by beta cells
- Glucose enters through glut2
- Glycolysis
- ATP inhibits K-ATPase : K+ trapped in
- Depolarization
- VDCC open
- Release of insulin granules
- VDK+ channels drive repolarization
Pharmacological inhibition of insulin secretion
diazoxid
Pharmacological stimulation of insulin secretion
sulphonyl urea (binds to K-ATP SU)
What does the insulin receptor recruit after autophosphorylation?
IRS-1
What 2 pathways can IRS1 activate?
- MAP kinase pathway
- PI3K pathway
What does the map kinase pathway result in?
mitogenic signals
What does PI3K pathway result in?
activation of PKB and PKC
What do PKB and PKC do?
phosphorylate rab4
What does rab4 do? (2)
- release GLUT4 vesicles
- increase glycolysis
Effect of insulin on intermediary metabolism in liver (4)
- increase glycolysis
- increase glycogenesis
- decrease glycogenolysis
- decrease gluconeogenesis
Effect of insulin on skeletal muscle IM (4)
- increase glycolysis
- increase protein anabolic effect
- increase glycogenesis
- decrease FFA and ketone bodies use
Effect of insulin on adipose tissue (3)
- clears lipids from plasma
- lipoprotein lipase increases breakdown of FFA
- decreases breakdown of TG
Overall anabolic effect of insulin (4)
- increase protein synthesis
- increase lipogenesis
- increase glycogenesis
- decrease gluconeogenesis
2 types of diabetes
type 1 : insulin dependant
type 2 : insulin independant
What is type 1 diabetes due to?
autoimmune destruction of beta cells
3 effects of type 1 diabets
- excessive glucose : osmotic diuresis
- ketone bodies : ketoacidosis, vomiting
What is type 2 diabetes due to?
- limitation of ability to produce enough insulin
- resistance to insulin
Treatment of type 2 diabetes?
- change diet
- exercise (glut4)
- sulfonylurea
- TZD (tiazolidin-dion drugs)
What does TZD do?
- decrease resistin secretion
- increase adiponectin secretion (decrease resistance)
3 diagnostic tests for diabetes
- Glucose tolerance test (fasting and 2 hours after ingesting glucose)
- Glycated Hb
- C peptide
