Glucose kinetics during acute and chronic treatment of rats with 2[6(4-chloro-phenoxy) hexyl]oxirane-2-carboxylate, etomoxir

Abstract

(1) The effects of 2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (etomoxir), a candidate antiketonaemic and antidiabetic drug, on glucose turnover and recycling of glucose carbon in rats were determined using [3- 3H,U- 14C]glucose. (2) Etomoxir (Na salt) was infused continuously at a rate of 2 mg/hr in fasted male Wistar ab Boots rats (250–280 g) that had been maintained on a standard diet, or on a diet containing 0.1% of etomoxir for 10 days. (3) In rats treated acutely with etomoxir, plasma glucose concentrations were decreased by about 1 mM, glucose turnover was decreased by 14%, and recycling of glucose carbon by 30% compared with the controls infused with 0.14 M NaCl. (4) Infusion of etomoxir in rats chronically pretreated with etomoxir had little effect on plasma glucose concentrations, but increased glucose turnover and recycling of glucose carbon by 40%. (5) Acute infusion of etomoxir caused dramatic lowering of blood 3-hydroxybutyrate concentrations from 1 mM to about 0.03 mM with little change in other intermediary metabolites. (6) In rats chronically fed etomoxir, the proportion of pyruvate dehydrogenase in quadriceps muscle in the active form was 31% compared with 15% in the controls. (7) It was concluded that etomoxir in the acute dose given had only moderate effects on glucose turnover and that chronic administration of etomoxir caused increased glucose turnover and glucose recycling in the rat.