Factors controlling pancreatic cell differentiation and function

Diabetes affects 4 to 5 % of the population worldwide and is the most commo n metabolic disorder. The number of individuals diagnosed with diabetes is rapidly increasing, especially in the developed countries and the disorder frequently leads to secondary complications such as retinopathy, nephropath y, neuropathy and cardiovascular disease. Type II (non-insulin-dependent) d iabetes mellitus is the most common form of diabetes, more than 90 % of dia gnosed cases, and results from insulin resistance, pancreatic beta-cell dys function, or a combination of both. The beta-cell dysfunction seems to resu lt in part from an inability of the beta cells to produce and secrete suffi cient amounts of active insulin in response to an increased demand for insu lin. Type I (insulin-dependent) diabetes mellitus is caused by an autoimmun e destruction of the insulin producing beta cells, resulting in insulin def iciency. The existing therapies for both types of diabetes are unsatisfacto ry since they do not offer a cure and are mostly not sufficient for prevent ing the secondary complications associated with diabetes. Thus, there is a great need for new improved therapies. This search is, however, hampered by our currently limited knowledge of the basic processes that control the pr oliferation, differentiation, survival and physiology of the beta cell. Ove r the last 7 to 8 years our knowledge concerning the development of the pan creas has increased substantially due to the use of genetically modified mi ce. Nevertheless, key questions regarding the control of proliferation and differentiation of pancreatic progenitor cells into fully functional beta c ells remain to be solved.