The glucagon-producing alpha cell: an electrophysiologically exceptional cell

Abstract

Activation of potassium channels normally serves to reduce cellular activity but recent data indicate that the glucagon-secreting alpha cells are different in this respect and that inhibition of voltage-gated potassium channels results in a paradoxical inhibition of glucagon secretion. Here we discuss these findings and attempt to provide a model for the regulation of glucagon secretion that incorporates these observations.

Simultaneous capillary electrophoresis competitive immunoassay for insulin, glucagon, and islet amyloid polypeptide secretion from mouse islets of Langerhans

“…It has been observed that α-cells are electrically active [33] and contain electrically active Ca 2+ channels [34]. Several reports have indicated that entry of extracellular Ca 2+ is required for glucagon release, whereas others have reported that glucagon can be released in the absence of Ca 2+ [35 – 37].…”

Patients With Long-QT Syndrome Caused by Impaired hERG -Encoded K v 11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated With Reactive Hypoglycemia

“…With inhibition of the K v current, there is no reactivation of the Na v channels and Ca v channels leading to a marked reduction of the action potential amplitude, thereby inhibiting glucagon release. As a consequence, glucagon secretion is decreased when K v channels are blocked 8,29,30 or dysfunctional as in LQT2 patients. Therefore, LQT2 patients have impaired counterregulatory defense against hypoglycemia.…”

ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic alpha and beta cells: similar functions but reciprocal effects on secretion

“…Reactivation of the Na + channels occurs during the interval between two successive action potentials and the inter-spike membrane potential, which in turn is influenced by the number of voltage-dependent K + channels activated during the action potential; the stronger the activation of K + channels, the more negative the inter-spike membrane potential and the greater the reactivation of Na + channels. This may explain the paradox that blocking voltage-gated K + channels in alpha cells is associated with inhibition of glucagon secretion and electrical activity rather than the stimulation seen in beta cells [49][50][51].…”