Beta Cells Flashcards
(8 cards)
Insulin secretion
phase 1 = acute release of readily releasable granules in response to calcium
phase 2 = requires continued replenishment of docked granules
- energy-dependent
- potentiation by hormones such as GLP1
Persistent hyperinsulinaemic hypoglycaemia of infancy
- neonates with hypoglycaemia and high insulin levels
- autosomal recessive or sporadic
- treated by glucose infusion or high sugar diet plus drugs to inhibit insulin release
- caused by lack of functional KATP
- PHHI mutations throughout SUR1 and a few in Kir6.2
- mutated SUR1 = truncated or misfolded protein = decreased expression = partially functional channels = not activated by metabolic inhibition
Neonatal diabetes
- within 6 months of birth
- transient or permanent
- may be associated with DEND syndrome
- commonly activating mutations in Kir6.2 and SUR1
- more channels open at resting ATP levels
- shifts ATP dose-response curve
- most treated with sulphonylureas
DEND syndrome
- developmental delay, epilepsy, neonatal diabetes
- Kir6.2 reduced ATP sensitivity
- increased channel opening
GLP1 and glucagon
GLP1 and glucagon produced by alternative processing of proglucagon:
- prohormone convertase 2 produces GRPP, glucagon and inactive GLP1 (position 1)
- prohormone convertase 1+3 produce GRPP, oxyntomodulin and active GLP1 (position 7)
- oxyntomodulin acts on both GLP1R and GIPR, but not very well on either
The incretin effect
- GLP1 and GIP are only released when glucose is taken in orally (not IV)
- result in increased insulin release
- antagonists suggest GIP may have a greater effect than GLP1
- GIP and GLP1 released as glucose is absorbed in the gut
Insulin, somatostatin and glucagon
glucagon - alpha
insulin - beta
somatostatin - delta
- insulin + somatostatin oscillate in phase
- they oscillate out of phase with glucagon
Effect of GPCRs on insulin release
Gq = IP3 = increased calcium = increased insulin release
Gs = cAMP = increased insulin release
Gi = reduced cAMP = reduced insulin release
cAMP = PKA = effects on beta cell
cAMP = cAMP-GEFII = effects on beta cell
