Abstract
The antidiabetic activity of pioglitazone was evaluated in spontaneously diabetic GK rats given a sucrose solution.In the rats given a 30% sucrose solution in addition to the stock diet and water, insulin resistance in the liver became more pronuonced and plasma glucose, insulin and triglyceride levels increased markedly as compared with those in the control rats given the stock diet and water alone.Furthermore, long-term sucrose solution-drinking aggravated the congenital defects in GK rats, such as glucose intolerance and dull insulin response to glucose, and decreased the pancreatic insulin content to 50% of that in the controls.Diabetic complications were also aggravated by drinking the sucrose solution: urinary albumin excretion increased, and motor nerve conduction velocity was delayed.When pioglitazone (3.2 mg/kg/day) was administered to the rats given the sucrose solution starting from the second week, the severity of the above mentioned diabetic states, which deteriorated in response to the sucrose drinking, was markedly reduced.The congenital defects in glucose metabolism and pancreatic function in GK rats were however not normalized. These findings suggest that pioglitazone can improve glucose and lipid metabolism by reducing insulin resistance in the liver.
