Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of Type 2 diabetes mellitus

There is increasing epidemiological evidence in humans which associates low birthweight with later metabolic disorders, including insulin resistance a nd glucose intolerance. There is evidence that nutritional and hormonal fac tors (e.g. maternal protein restriction, exposure to excess maternal glucoc orticoids) markedly influence intra-uterine growth and development. A pictu re is also emerging of the biochemical and physiological mechanisms that ma y underlie these effects. This review focuses on recent research directed t owards understanding the molecular basis of the relationship between indice s of poor early growth and the subsequent development of glucose intoleranc e and Type 2 diabetes mellitus using animal models that attempt to recreate the process of programming via an adverse intra-uterine or neonatal enviro nment. Emphasis is on the chain of events and potential mechanisms by which adverse adaptations affect pancreatic-p-cell insulin secretion and the sen sitivity to insulin of key metabolic processes, including hepatic glucose p roduction, skeletal-muscle glucose disposal and adipose-tissue lipolysis. U nravelling the molecular details involved in metabolic programming may prov ide new insights into the pathogenesis of impaired glucoregulation and Type 2 diabetes.