L4 - KATP and regulation of insulin secretion

how many genes are there in humans for the BK channel

one

what does a dendrogram show

evolutionary relationships

what does Kir mean

inwardly rectifying potassium channels

what type of potassium channels are likely most similar to the first potassium channels seen in bacteria

inward rectifiers (2TM(P))

what is a main role of the KATP channel

controlling insulin secretion

give a description of the beta cell and ion channels at low glucose levels

level of metabolism low, low ATP, higher mgADP (this promotes channel opening by the SUR1 subunit), potassium channels are open, allowing hyperpolarisation, L-type calcium channels are closed, no electrical activity, no insulin secretion

describe ion channels in beta cells when there is high glucose

glucose enters the cell, drives metabolism and therefore production of ATP, ATP binds Kir6.2 causing inhibition/closing the channel, inside of cell becomes depolarised due to less potassium efflux, L-type calcium channels open, calcium enters, triggering release of insulin, insulin tells target cells to metabolise or take up glucose

what is a common use of sulphonylureas

to treat diabetes

what does azide do

inhibit ATP production

what does low blood sugar cause in terms of insulin secretion and KATP activity

reduces insulin secretion, increases KATP activity

what does high blood sugar do in terms of insulin secretion and KATP activity

increases insulin secretion, turns off KATP channels

what KATP activity results in hyperinsulinism

low KATP activity

what KATP activity results in neonatal diabetes mellitus

high KATP activity

what are the characteristics of neonatal diabetes mellitus

low insulin secretion with poor response to glucose, rare and usually presents within 6-9 months of birth, gain of function mutations in Kir6.2 or SUR1, reduced ability of ATP to bind Kir6.2, 90% of patients can be treated with sulfonylureas

what are the characteristics of congenital hyperinsulinism

rare, unregulated high insulin secretion even when glucose is low, presents as severe life threatening hypoglycemia just after birth, loss of function mutations in Kir6.2 or SUR1, few or low active KATP, some can be treated with KATP activators if some channel is present, this is harder because some patients do not have enough/any channels

what regulates Kir6.2

ATP binds and inhibits (closes) the channel

what regulates SUR1

MgADP promotes channel opening