The novel imidazoline compound BL11282 potentiates glucose-induced insulinsecretion in pancreatic beta-cells in the absence of modulation of K-ATP channel activity
Am. Efanov et al., The novel imidazoline compound BL11282 potentiates glucose-induced insulinsecretion in pancreatic beta-cells in the absence of modulation of K-ATP channel activity, DIABETES, 50(4), 2001, pp. 797-802
The insulinotropic activity of the novel imidazoline compound BL11282 was i
nvestigated. Intravenous administration of BL11282 (0.3 mg . kg(-1) . min(-
1)) to anesthetized rats did not change blood glucose and insulin levels un
der basal conditions, but produced a higher increase in blood insulin level
s and a faster glucose removal. from the blood after glucose infusion. Simi
larly, in isolated Wistar rat pancreatic islets, 0.1-100 mu mol/l BL11282 p
otently stimulated glucose-induced insulin secretion but did not modulate b
asal insulin secretion. Unlike previously described imidazolines, BL11282 d
id not block ATP-dependent K+ channels. Furthermore, the compound stimulate
d insulin secretion in islets depolarized with high concentrations of KCl o
r permeabilized with electric shock. Insulinotropic activity of BL11282 was
dependent on activity of protein kinases A and C, In pancreatic islets fro
m spontaneously diabetic GK rats, the imidazoline compound restored the imp
aired insulin response to glucose. In conclusion, the imidazoline BL11282 c
onstitutes a new class of insulinotropic compounds that exerts an exclusive
glucose-dependent insulinotropic activity in pancreatic islets by stimulat
ing insulin exocytosis.