Targeting the pancreatic β-cell to treat diabetes

The pancreatic β-cell is a key regulator of glucose homeostasis, sensing blood glucose levels after a meal and secreting insulin appropriately.Loss of β-cell number and function feature prominently in both type 1 and type 2 diabetes.Promoting β-cell regeneration, survival or function, especially with small molecules, may prove to be an effective strategy for treating diabetes.β-cell regeneration can be accomplished by stimulating the division of existing β-cells. It will be important, however, to induce proliferation in a cell-specific manner to avoid oncogenic transformation.Another mechanism for β-cell regeneration is through cellular reprogramming. Such transformations can occur from stem-cell-like populations (directed differentiation) or from other terminally differentiated cell types (transdifferentiation).Prevention or slowing of β-cell death in the first place may avoid the loss of β-cell mass that enables the transition from insulin resistance to overt diabetes.Promoting glucose-dependent induction of insulin secretion would restore hormone levels following β-cell death. Compounds exist to enhance insulin secretion, but many are not glucose-dependent.Technical challenges to identifying novel compounds include a lack of many good human cell lines and the development of sophisticated techniques to measure β-cell function and number for high-throughput screening.