TRPC5: a new entry to the chromaffin cell's palette of ion channels that control adrenal response to hypoglycemia.

Regulation of glucose levels during insulin-evoked hypoglycemia is impaired in patients with diabetes and can lead to a condition called hypoglycemia-associated autonomic failure (HAAF). The underlying mechanism of the reduced sympathoadrenal response in HAAF patients to counteract hypoglycemia is not yet clarified. In this issue of , Bröker-Lai et al, show that mice lacking TRPC5 channels possess an impaired response to insulin-induced hypoglycemia similar to humans with HAAF. The altered response is due to a reduced release of adrenaline from chromaffin cells lacking functional TRPC5 channels activated by ACh and PACAP, the neurotransmitters released during sympathetic stimulation. Their work highlights a novel cell signaling pathway in which stimulation of PAC1 and muscarinic M1 receptors activate TRPC5 channels to induce sustained adrenaline secretion during the adrenergic counter-response to hypoglycemia.