Anatomical versus functional β-cell mass in experimental diabetes

Abstract

The ability of pancreatic β-cell mass to vary according to insulin requirements is an important component of optimal long-term control of glucose homeostasis. It is generally assumed that alteration of this property largely contributes to the impairment of insulin secretion in type 2 diabetes. However, data in humans are scarce and it is impossible to correlate β-cell mass and function with the various stages of the disease. Thus, the importance of animal models is obvious. In rodents, increased β-cell mass associated with an increase in the function of individual β-cells contributes to the adaptation of the insulin response to insulin resistance in late pregnancy and in obesity. A reduction in β-cell mass always corresponds to an alteration in insulin secretory capacity of islet tissue (Zucker diabetic fatty and Goto-Kakisaki rats, db/db mice). During regenerative processes following experimental reduction of β-cell mass [partial pancreatectomy, streptozocin (STZ) injection], β-cell mass increase is not associated with a corresponding improvement of β-cell function, thus indicating that regenerative β-cells did not achieve functional maturity. The main lesson from experimental diabetes is therefore that β-cell mass cannot always predict functional capacity of the β-cell tissue and that the functional β-cell mass rather than the anatomical β-cell mass must be taken into account at all times. © 2008 The Authors Journal Compilation © 2008 Blackwell Publishing Ltd.