Glucose sensing in pancreatic beta-cells - A model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus

Nutrient homeostasis is known to be regulated by pancreatic islet tissue. T he function of islet beta -cells is controlled by a glucose sensor that ope rates at physiological glucose concentrations and acts in synergy with sign als that integrate messages originating from hypothalamic neurons and endoc rine cells in gut and pancreas. Evidence exists that the extrapancreatic ce lls producing and secreting these (neuro)endocrine signals also exhibit a g lucose sensor and an ability to integrate nutrient and (neuro)hormonal mess ages. Similarities in these cellular and molecular pathways provide a basis for a network of coordinated functions between distant cell groups, which is necessary for an appropriate control of nutrient homeostasis. The glucos e sensor seems to be a fundamental component of these control mechanisms. I ts molecular characterization is most advanced in pancreatic beta -cells, w ith important roles for glucokinase and mitochondrial oxidative fluxes in t he regulation of ATP-sensitive K+ channels. Other glucose-sensitive cells i n the endocrine pancreas, hypothalamus, and gut were found to share some of these molecular characteristics. We propose that similar metabolic signali ng pathways influence the function of pancreatic alpha -cells, hypothalamic neurons, and gastrointestinal endocrine and neural cells.