Indomethacin Decreases Insulin Secretion in Patients with Type 2 Diabetes Mellitus

Abstract

In healthy subjects, basal endogenous glucose production (EGP) is partly regulated by paracrine intrahepatic factors. Administration of indomethacin, an inhibitor of prostaglandin synthesis, resulted in a transient stimulation of EGP without changes in glucoregulatory hormone concentrations. It is unknown whether similar paracrine factors influence basal EGP in type 2 diabetes mellitus. The effects of 150 mg indomethacin, a nonendocrine stimulator of glucose production in healthy adults, and placebo on EGP were measured in a randomized placebo-controlled study in patients with type 2 diabetes mellitus (3 men and 3 women; mean age, 58.5 years; mean body mass index, 28.6 kg x m(-2)). EGP was measured before and for 6 hours after administration of placebo/indomethacin, by a primed, continuous infusion of [6,6-2H2]glucose. After indomethacin, plasma glucose and EGP increased in all subjects by 14% (P < .05) and 48% (P < .05), respectively. In the control experiment, plasma glucose and EGP declined gradually in all subjects by 22% (P < .001) and 17% (P = .004), respectively. The stimulation of glucose production coincided with the inhibition of insulin secretion by 52% within 1 hour after administration of indomethacin (P < .001). In the control experiment, insulin secretion decreased gradually by 18% after 6 hours (P < .001). Thus, indomethacin inhibits insulin secretion and stimulates EGP in type 2 diabetes.