EFFECT OF N-HEXACOSANOL ON INSULIN-SECRETION IN THE RAT

n-Hexacosanol, a long-chain satured fatty alcohol extracted from Hygro phyla erecta Hochr., has been recently shown to exert neurotrophic pro perties on central neurons and to stimulate phagocytosis in macrophage s. The present work was designed to investigate the effects of hexacos anol on stimulated insulin secretion in vivo and in vitro. In anaesthe tized rats, hexacosanol (2 mg/kg i.p.) induced a reduction of the insu lin response to an intravenous glucose tolerance test (0.3 g/kg) with a consequent increase in hyperglycaemia. In vitro, in the isolated per fused pancreas, hexacosanol at the concentration of 10(-7) M clearly r educed the two phases of glucose-induced insulin secretion. At the hig her concentration (10(-5) M), hexacosanol was no longer able to exert an inhibition of glucose-induced insulin release; surprisingly a stimu lating effect occurred which was of the same magnitude as in control e xperiments with Tween alone, at the concentration used to dissolve hex acosanol. In isolated perifused islets, 22 mM glucose-stimulated insul in release was also inhibited by hexacosanol at the concentrations of 10(-9) M and 10(-7) M, but not at 10(-5) M. In contrast, insulin secre tion induced by arginine (20 mM) was not affected by the different con centrations of hexacosanol. It is concluded that n-hexacosanol at 10(- 9) M and 10(-7) M exerts an inhibitory effect on insulin secretion sti mulated by glucose in vivo and in vitro in the rat, suggesting a direc t effect on islets of Langerhans.