Aminophylline stimulates insulin secretion in patients with type 2 diabetes mellitus

In healthy subjects, paracrine factors partly regulate insulin secretion an d basal endogenous glucose production. Administration of pentoxifylline, an adenosine receptor antagonist, inhibits transiently endogenous glucose pro duction in healthy humans without any changes in glucoregulatory hormone co ncentrations. To evaluate the modulatory role of adenosine on endogenous gl ucose production and basal insulin secretion in type 2 diabetes, aminophyll ine, a potent adenosine receptor antagonist, was administered intravenously to 5 patients with type 2 diabetes mellitus in a saline-controlled study. Endogenous glucose production was measured before and during 6 hours after administration of aminophylline/saline by primed, continuous infusion of [6 ,6-H-2(2)]glucose. During both experiments, the decrease in plasma glucose concentration was similar (16% v 18% from basal, not significant [NS]). Aft er aminophylline administration, basal endogenous glucose production was tr ansiently inhibited within 15 minutes to 70% from basal, whereas it did not change significantly in the control experiment (P = .02). The inhibition o f glucose production coincided with stimulation of insulin secretion to 144 % from basal 90 minutes after the administration of aminophylline (P = .008 ). In the control experiment insulin secretion decreased gradually by 29% d uring 6 hours. We conclude that aminophylline inhibits endogenous glucose p roduction in type 2 diabetes by stimulation of insulin secretion. Paracrine factors, such as adenosine, may be involved in the regulation of basal ins ulin secretion in type 2 diabetes mellitus. Copyright (C) 2001 by W.B. Saun ders Company.