分子与遗传医学

Prevention and Treatment of Obesity and Diabetes and their Related Complications

Abstract

Moon K Song, David S Bischoff, Koichi Uyemura, Albert M Song and Dean T Yamaguchi

This review article evaluates the current knowledge in the prevention and treatment of diabetes and obesity. The relative abundance of food and lack of rigorous exercise common in modern life pose serious challenges in the incidence and treatment of these diseases and their complications. Although blood glucose controlling agents such as insulin and oral hypoglycemic agents are available, most currently available drugs have been shown to exhibit minimal to moderate efficacy and many of them have serious side effects. For example, rosiglitazone and pioglitazone are often prescribed to improve insulin sensitivity by increasing expression of glucose transporter-4 in muscle and fat cells; however, they can frequently induce cardiovascular complication and liver damage. Similarly, available anti-obesity drugs have not been very effective in reducing obesity and also exhibit many common side effects. We are presently testing a new drug, Cyclo (his-pro) plus zinc (Cyclo-Z), which prevents and treats diabetes without any known side effects. It is also very effective in animals and humans in the control of body weight. Our studies have shown that Cyclo-Z improves insulin sensitivity as measured by oral glucose tolerance test (OGTT), decreases fasting and postprandial blood glucose, diminishes HbA1C, and reduces body weight significantly in diabetic and obese rats and humans. Studies in Goto-Kakizaki rats, a genetic model of type 2 diabetic rats, and genetically obese diabetic ob/ob mice have confirmed the ability of Cyclo-Z to improve diabetes-related clinical abnormalities and to decrease body mass index in animals. Furthermore, we have successfully completed FDAIND approved phase 1 and phase 2a clinical trials for the treatment of diabetes alone and are currently awaiting the conclusion of another phase 2a clinical trial with obese diabetic subjects. In this paper we summarize the currently available diabetes and obesity therapies and review our studies to illustrate the effective and safe ability of Cyclo-Z to reduce and treat patients suffering from diabetes and obesity.