Week 4 Flashcards
1
Q
What is the function of insulin?
A
- Stimulation of glucose uptake by cells from systemic circulation
- Suppression of hepatic gluconeogenesis
-(generation of glucose from non-
carbohydrate sources) - Suppression of glycogenolysis
- breakdown of glycogen to
glucose in muscle and liver
REGULATE GLUCOSE HOMEOSTASIS
2
Q
What two polypeptide chains does the insulin molecule have?
A
- A chain (21 aa) and B chain (30aa)
- Linked by two disulphide bridges
3
Q
What chromosome is insulin gene located?
A
Chromosome 11
4
Q
Breakdown the insulin biosynthesis
A
- mRNA transcription
- Excision of intervening sequence
- Translation of mRNA (L,B,C,A) = pre proinsulin
-transport of pre-proinsulin to lumen
of ER- (L signal peptide)
3. Signaal peptide (L) removed = proinsulin Contains three chains A B C Disulfide bonds and amino acids links hold chains together
- Pro insulin goes through golgi compartments
Endopeptidases cleave Lys‐Arg and Arg‐Arg- Carboxypeptidases cleave off terminal Lys
and Arg amino acids
- Liberate C‐peptide
= final insulin consisting of A and B chains held
together by disulfide bond
- Carboxypeptidases cleave off terminal Lys
5
Q
How is insulin secrected?
A
- Co‐precipitates with zinc ions as microcrystals in secretory granules
- Microtubules transport granules to plasma membrane
- Granules are released by exocytosis
6
Q
What happens when glucose is increase (e.g. you just ate a meal)
A
- Glucose binds to GLUT-2 receptor on plasma membrane and enters the cell
- glucose is converted to glucose-6-phosphate via glycolysis
- glucose will be metabolised to generate a lot of ATP
- ATP triggers ATP-sensitive K+ channel to block channel, so K+ in cell goes up and results in depolarisation
- voltaged gated calcium channel is triggered to open and allow calcium into the cell. Triggers vesicles that contain insulin to be transported to plasma membrane and released into blood stream.
7
Q
What does an insulin receptor contain?
A
4 subunits (two alpha and two beta) Tyrosine kinase
8
Q
What happens when insulin binds?
A
When insulin binds we get:
- Autphosphorylation of the tyosine residues of the receptor (aka becomes phosphorylated the tyrosine kinase)
- once phophorylated binds to protein IRS
- the IRS becomes phosphorylated
9
Q
Explain what happens to P13K and the cascade of events
A
- PI3K converts PIP2 to PIP3
- Phosphatidylinositol 4,5‐bisphosphate
- Phosphatidylinositol (3,4,5)‐trisphosphate
- PIP3 activates protein kinase B (PKB/Akt) via its PH domain
- PIP3 activates phosphatidylinositol dependant protein kinase (PDK1) via PH domain
- PDK1 phosphorylates PKB/Akt, releases it to the cytosol and nucleus for signaling
10
Q
Name the three events that PKB/Akt activates
A
- Gluocse uptake by glucose transporters ( GLUT4)
- Protein synthesis
-Stimulation of glycogen synthase
> conversion of glucose to glycogen (storage)
- Protein synthesis
11
Q
Summary of insulin receptor action
A
- Phosphorylation of insulin receptor (its a tyrosine kinase)
- IRS-1 is phosphorylated
- IRS-1 binds P13K: phosphorylates phospholipids to PIP3
- PIP3 recruits PDK1 and PKB/Akt to the membrane
- PKB/Akt releases to activate signalling pathways