INSULIN RELEASE IN TYPE-2 DIABETES-MELLITUS

Impaired insulin response is a characteristic feature of Type 2 diabetes. Overt diabetes develops when beta-cells fail to release enough insulin to compensate for decreased insulin sensitivity. However, a subgroup Of normal weight patients demonstrates a pronounced beta-cell secretory defect and a normal insulin sensitivity. The molecular basis behind the impaired insulin response in Type 2 diabetes is not cleat. Our studies in two animal models of this disease (CK rat and ob/ob mouse) suggest that an impaired glucose metabolism may be a primary defect in the stimulus-secretion coupling in the beta-cells in Type 2 diabetes. In the GK rat, three major alterations in the islet metabolism of glucose have been demonstrated : 1) increased glucose utilization but unchanged glucose oxidation; 2) increased glucose cycling and 3) decreased activity of the glycerol phosphate shuttle. In ob/ob animals we have found an increased rate of glucose cycling. These derangement might result in an incomplete closure of ATP-sensitive K+-channels with a decreased insulin response as a consequence.