Towards gene therapy of diabetes

. Type I diabetes, also knownas insulin-dependent diabetes mellitus (IDDM) or juvenile-onset dia-betes, is characterized by the autoimmune destruction of pancreaticb-cells. Type II diabetes, also known as non-insulin-dependent dia-betes mellitus (NIDDM) or adult-onset diabetes, is a complex diseasecharacterized by end-organ unresponsiveness to the effects of insulin,as well as by b-cell dysfunction and eventual b-cell failure. Theunique aspect of type I diabetes is autoimmune b-celldestruction,whereas the unique aspect of type II diabetes is decreased end-organresponsiveness to insulin. Both forms share the characteristics of lossof b-cellfunction (although this occurs more prominently and earlierin type I than in type II) and peripheral organ damage caused by thetoxic effects of hyperglycemia.For both type I and type II diabetes, the major clinical problems result from the long-term effects of chronic hyperglycemia, which occurs because standard therapy for diabetes cannot maintain bloodglucose concentrations within the relatively narrow range that isfound in the presence of a normally functioning pancreas. Althoughincompletely understood, it is thought that hyperglycemia leads to theformation of high levels of highly reactive advanced glycation end-products(AGEs)