Anatomical versus functional β‐cell mass in experimental diabetes

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.