Glucose Transport Regulators

The prevalence of Type 2 diabetes (Non-Insulin-Dependent Diabetes Mellitus) increases at an alarming rate in the world's population, reaching an epidemic proportion. Moreover, impaired glucose tolerance and insulin resistance are being diagnosed nowadays in a growing subpopulation of obese children and adolescents, mostly in Western societies. This adds to the concern that not only the number of NIDDM patients will increase dramatically to over 300 millions within 20 years, but also that overt diabetes and diabetes-related complications will develop earlier in life. The main goal of pharmacological therapy of diabetic patients is to reduce blood glucose levels to the normal range. Indeed, most diabetic patients require oral antihyperglycemic drug therapy; yet, the relatively high rate of failure of these drugs and the chronic nature of the disease, which is associated with progressive dysfunction and exhaustion of pancreatic insulinproducing β-cells, lead in many cases to insulin therapy. Most available antihyperglycemic drugs sensitize β-cells to secrete insulin or overcome peripheral insulin resistance by sensitizing insulin-responsive tissues towards insulin. Nevertheless, genuine insulin mimetic drugs or drugs aimed at directly augmenting the glucose transport system in insulinsensitive tissues are still being sought. This review describes briefly current molecular targets for antihyperglycemic drugs and discusses potential compounds that may act as insulin-mimetics or enhancers. In addition, a novel concept is introduced for the development of carbohydrate derivatives that may augment glucose transport in insulin-sensitive tissues in an insulin-independent manner.