Aberrant energy metabolism is one characteristic of diabetes mellitus (DM). Two types of DM have been identified, type 1 and type 2. Most of type 2 DM patients eventually become insulin dependent because insulin secretion by the islets of Langerhans becomes exhausted. In the present study, we show that resveratrol (3,5,4'-trihydroxylstilbene) possesses hypoglycemic and hypolipidemic effects in streptozotocin-induced DM (STZ-DM) rats. In resveratrol-treated STZ-DM rats, the plasma glucose concentration on day 14 was reduced by 25.3 +/- 4.2%, and the triglyceride concentration was reduced by 50.2 +/- 3.2% compared with the vehicle-treated rats. In STZ-nicotinamide DM rats, the plasma glucose concentration on day 14 was reduced by 20.3 +/- 4.2%, and the triglyceride concentration was reduced by 33.3 +/- 2.2% compared with the vehicle-treated rats. Resveratrol administration ameliorates common DM symptoms, such as body weight loss, polyphagia, and polydipsia. In STZ-nicotinamide DM rats, resveratrol administration significantly decreased insulin secretion and delayed the onset of insulin resistance. Further studies showed that glucose uptake by hepatocytes, adipocytes, and skeletal muscle and hepatic glycogen synthesis were all stimulated by resveratrol treatment. Because the stimulation of glucose uptake was not attenuated in the presence of an optimal amount of insulin in insulin-responsive cells, the antihyperglycemic effect of resveratrol appeared to act through a mechanism(s) different from that of insulin.

The incidence of gallstone is higher in patients with diabetes mellitus than in general population. It is generally attributed to hypomotility and lowered emptying function of the gallbladder. In this study, we investigate if chronic hyperglycemia is correlated with reduced contractile function of the bile ducts in rat. Hyperglycemic rats were induced by streptozotocin-nicotinamide treatment. Hyperglycemic rats were sacrificed eight months after induction and bile ducts were removed for the subsequent studies. The bile duct contractility of the normal rats is consistently higher than that of the hyperglycemic rats. The contractities were measured to be 5.5 ± 0.2 mg vs. 4.2 ± 0.1 mg without CCK stimulation, and 5.5 ± 0.3 mg vs. 7.9 ± 0.4 mg with CCK stimulation, respectively for hyperglycemic and normal rats. There was no significant difference in plasma CCK concentration in hyperglycemic rats and normal rats. The expression of CCK-A receptor protein in the bile duct tissue was decreased in hyperglycemic rats compared with that of the normal rats, and it may, at least in part, responsible for a reduced contractility. A reduced bile duct motility may cause bile retention, and may be one of the factors predispose to gallstone formation in type 2 diabetes patients, which is characterized with chronic hyperglycemia.