STIMULATION OF INSULIN-SECRETION BY GLUCOSE IN THE ABSENCE OF DIMINISHED POTASSIUM (RB-86(+)) PERMEABILITY

Two inhibitors of the nucleotide-sensitive K+ (K(ATP)) channel, tolbutamide and quinine, were utilized in order to assess the role of this channel in glucose-stimulated insulin release from perifused rat islets. In the absence of these drugs, the addition of 15 mM glucose elicited a marked biphasic stimulation of insulin secretion concomitant with a reduction in the rate of Rb-86+ efflux. In the presence of either 500-mu-M tolbutamide or 100-mu-M quinine, a reduced rate of efflux of Rb-86+ was observed together with an elevated rate of insulin release. Under such conditions, the addition of 15 mM glucose retained the ability to stimulate insulin secretion though this was associated with a marked increase in Rb-86+ efflux. It is concluded that a net reduction of beta-cell K+ permeability is not an obligatory step in glucose-stimulated insulin release. Thus, glucose is likely to exert depolarizing actions on the beta-cell in addition to the closure of K+ channels.