Beneficial effect of long-term combined treatment with voglibose and pioglitazone on pancreatic islet function of genetically diabetic GK rats

Effects of voglibose (an alpha-glucosidase inhibitor) and pioglitazone tan insulin sensitizer) on glycemic control and on the function of pancreatic i slets were evaluated using Goto-Kakizaki (GK) rats with non-insulin-depende nt diabetes mellitus (NIDDM). Five week administration (8-13 weeks of age i n GK rats) of voglibose alone (added to the chow at a concentration of 10 p pm), pioglitazone alone (10 mg/kg daily p.o.), or both of the agents togeth er significantly improved fasting plasma glucose levels and those at 120 mi n in oral glucose tolerance tests. Insulin secretory capacity in response t o glucose of the isolated islets, assessed by batch incubation, was signifi cantly improved in the voglibose and in the voglibose plus pioglitazone gro ups. Eight-week administration (5-13 weeks of age) of voglibose and voglibo se plus pioglitazone successfully lowered the fasting levels of plasma gluc ose and triglyceride. The glucose-responsiveness in insulin release from th e islets was also significantly recovered by the therapy. The treatment inc reased the insulin content of the islets to almost twice that in untreated controls. Thus, treatment by these drugs can not only effectively ameliorat e the metabolic derangement of NIDDM in GK rats, but it can also restore th e deteriorated islet function, possibly through protection from glucose tox icity.