Role of G proteins in K(ATP) channel modulation by the neuropeptide somatostatin

Glucose-induced insulin secretion from the pancreatic β cell is initiated by a reduction of ATP-sensitive K+ [K(ATP)] channel activity. It was hypothesized that somatostatin (SRIF)-induced inhibition of insulin release is mediated via an increase in K(ATP) channel activity. Patch-clamp studies demonstrated that SRIF stimulates K(ATP) activity and further indicated that this mechanism involves a pertussis toxin-sensitive G protein. However, low concentrations of glucose reversed SRIF-mediated K(ATP) stimulation, indicating that inhibition of insulin secretion by SRIF is not mediated via its effect on K(ATP). On the basis of preliminary experiments it is proposed that the inhibition of secretion by SRIF is due to a G protein-induced decrease in calcium channel activity.