The genetically endowed quality of -cells determines their potential to cope with nutritionally enhanced insulinogenesis. Certain species may respond to the inherent hyperphagia with long-lasting compensatory insulin secretion entailing obesity. Other animal species and certain human populations with labile pancreas are unable to maintain the hypersecretion of insulin in response to the imposed nutrient load, thus causing the transition from type 2 to type 1 diabetes. Insulin resistance is most probably an inherited trait proximal to the insulin receptor responsible for the cellular signaling defect that leads to the development of type 2 diabetes with the possibility of consequent -cell failure in both animals and humans. The impaired glucose tolerance and hyperglycemia should not be considered as markers of -cell function, but as an incitement of oversecretion culminating in apoptosis.
Apoptosis is a pathophysiologic process distinct from, and preceding, necrosis.
Insulin resistance can be reversed and apoptosis prevented by reducing the nutritionally induced hyperglycemia in time. Psammomys obesus illustrates this course of events and is an excellent model of human transition from type 2 to type 1 diabetes, demonstrating the reversibility of the process and manifesting -cell nuclear fragmentation, which causes a failure of biosynthetic capacity in the final stage of nutritionally induced diabetes.