Endocrine pancreas plasticity under physiological and pathological conditions.

Abstract

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, in association with beta-cell hyperactivity, contributes to insulin oversecretion in response to insulin resistance. There is increasing evidence that the ability of the beta-cell mass to expand in adult mammals is much higher than previously thought. During pregnancy, placental hormones, especially placental lactogens, are mainly responsible for the changes in beta-cell mass. The factors involved in beta-cell growth in obesity are far from clear, although increased free fatty acids seem to be the main candidate. Many 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 prevailing insulin demand. This defect may originate from genetic predisposition, but the situation is likely worsened by environmental factors such as hyperglycemia (glucotoxicity) and hyperlipidemia (lipotoxicity). Better understanding of beta-cell growth and regeneration mechanisms may allow new strategies in the treatment of type 2 diabetes based on early limitation of beta-cell damage and/or restoration of a functional beta-cell mass.