EMBRYONIC DEVELOPMENT OF β CELLS

Many aspects of human physiology are regulated by insulin, a hormone produced exclusively by β cells of the pancreas. Insulin insufficiency is the cause of type I diabetes, where β cells are selectively destroyed by autoimmune attack, and type II diabetes, where normal insulin supplies fail to meet demand due to impaired insulin sensitivity in peripheral organs and β-cell fail-ure (Bell and Polonsky 2001). Although both types of diabetes can be treated effectively by insulin injections, the long-term health of diabetic patients appears to crit-ically depend on how insulin is delivered (Kahn 2004; Daneman 2006). Continuous release in a measured fashion relative to physiological glucose levels is clearly beneficial. So far, attempts to mechanically mimic the action of β cells have fallen short; evolution has produced a cell with exquisite sensitivity, response time, and capacity to measure glucose and release insulin in a physiological manner (Kahn 2004). The best way to supply insulin is clearly to use β cells. Type I diabetes patients could to benefit from a supply of new β cells. Although the cause of type I diabetes is autoimmune attack on β cell and a cure requires under-standing and stopping autoimmunity, transplanted cadav-eric islets have demonstrated impressive relief from diabetic symptoms (Lakey et al. 2006). The demand for transplantable new β cells, however, far outstrips available supplies. In addition, it would be ideal to supply autologous β cells to eliminate the need for immunosuppression (in the case of Type II diabetes; for Type I, blocking the autoim-mune attack remains a key hurdle). Over the years, several strategies to produce new β cells have been proposed. These include directed differentiation from embryonic stem (ES) cells, proliferation of existing β cells, derivation from putative adult endocrine progenitor cells, and more recently, reprogramming of non-β cells to β cells. Each of these strategies exploits a different aspect of β-cell biology. Although notable progress has been made, significant chal-lenges remain and discoveries will be needed in order to translate this research into therapy. Here, we briefly review key areas of β-cell development and critically evaluate the current approaches to produce new β cells