Glucose, regulator of survival and phenotype of pancreatic beta cells

The key role of glucose in regulating insulin release by the pancreatic beta cell population is not only dependent on acute stimulus-secretion coupling mechanisms but also on more long-term influences on beta cell survival and phenotype. Glucose serves as a major survival factor for beta cells via at least three actions: it prevents an oxidative redox state, it suppresses a mitochondrial apoptotic program that is triggered at reduced mitochondrial metabolic activity and it induces genes needed for the cellular responsiveness to glucose and to growth factors. Glucose-regulated pathways may link protein synthetic and proliferative activities, making glucose a permissive factor for beta cell proliferation, in check with metabolic needs. Conditions of inadequate glucose metabolism in beta cells are not only leading to deregulation of acute secretory responses but should also be considered as causes for increased apoptosis and reduced formation of beta cells, and loss of their normal differentiated state.