Decreased insulin secretion in type 2 diabetes: A problem of cellular massor function?

Type 2 diabetes is characterized by diminished or inappropriate secretion o f insulin, which could be a defect of either islet cell function or beta -c ell mass. Quantitation of islet cell populations in postmortem pancreas dem onstrates little change of beta -cell mass in type 2 diabetes. Reduction of islet cell mass (up to 30%) is associated largely with islet amyloid depos ition, and the degree of amyloidosis is independent of the duration of the disease. Insulin secretory capacity is dependent on both function and mass of cells. beta -Cell secretion is heterogeneous; increasing glucose concent rations result in recruitment of beta -cells into the secretory pool, indic ating a large reserve of secretory capacity that can be recruited in insuli n resistant conditions. The Starling curve of islet function describes the relationship of insulin secretion to increasing levels of insulin resistanc e and hyperglycemia in type 2 diabetes. Longitudinal studies in Macaca mula tta monkeys show that insulin resistance is accompanied by increased islet mass and onset of diabetes is associated with deposition of amyloid and red uction of beta -cells. Increasing the function of unresponsive beta -cells rather than the mass of cells may be a more effective therapeutic target fo r type 2 diabetes.