Endocrine pancreas plasticity under physiological and pathological conditions

Endocrine pancreas plasticity may be defined as the ability of the organ to adapt the beta -cell mass to the variations in insulin demand. For example , during late pregnancy and obesity, the increase of the beta -cell mass, i n association with beta -cell hyperactivity, contributes to insulin oversec retion in response to insulin resistance. There is increasing evidence that the ability of the beta -cell mass to expand in adult mammals is much high er than previously thought. During pregnancy, placental hormones, especiall y placental lactogens, are mainly responsible for the changes in beta -cell mass. The factors involved in beta -cell growth in obesity are far from cl ear, although increased free fatty acids seem to be the main candidate. Man y data suggest that the impairment of insulin secretion in type 2 diabetes is partly related to reduction of beta -cell mass, at least relative to pre vailing insulin demand. This defect may originate from genetic predispositi on, but the situation is likely worsened by environmental factors such as h yperglycemia (glucotoxicity) and hyperlipidemia (lipotoxicity). Better unde rstanding of beta -cell growth and regeneration mechanisms may allow new st rategies in the treatment of type 2 diabetes based on early limitation of b eta -cell damage and/or restoration of a functional beta -cell mass.