Metabolic regulation of insulin secretion in health and disease

Despite the current media focus, Covid-19 is not the only current pandemic There is also a global pandemic of diabetes It is caused by an insufficiency of the hormone insulin, which lowers blood glucose levels Here we highlight recent work that addresses the question of how insulin is normally secreted from the β-cells of the pancreas and what goes wrong with this process in diabetes We focus on the metabolic regulation of the ATP-sensitive potassium channel, an ATP-gated membrane pore that regulates insulin secretion We show that when this pore is shut, insulin is released, and when it is open, insulin release is prevented As may be expected, genetic mutations that impair the ability of ATP to close the channel cause neonatal diabetes We also consider if a failure of β-cell metabolism to generate enough ATP to close the channel may lead to the progressive decline in β-cell function in type 2 diabetes © 2021 The Authors Published by Portland Press Limited All Rights Reserved