title: Insulin release: reconciliation of the receptor and metabolic hypotheses. Nutrient receptors in islet cells.
abstract: Nutrients which stimulate insulin secretion are currently thought to initiate the series of cellular events eventually leading to insulin release either by interacting with a stereospecific receptor system (the regulatory site hypothesis) or by acting as a fuel (the substrate site hypothesis) in the pancreatic B-cell. The latter hypothesis is supported by a number of observations indicating that the capacity of nutrients to stimulate insulin release is indeed highly dependent on their capacity to increase catabolic fluxes in isolated pancreatic islets. However, these observations do not rule out the existence of nutrient receptors in islet cells. For instance, a nonmetabolized analog of L-leucine stimulates insulin release by causing allosteric activation of glutamate dehydrogenase, which should be considered, therefore, as a receptor for certain amino acids. Likewise, the increase in glycolytic flux, which is associated with the process of glucose-stimulated insulin release, is attributable not solely to a mass action phenomenon but also to the activation of phosphofructokinase by fructose 2.6-bisphosphate. The biosynthesis of this activator may involve a glucose receptor system. The fact that certain nutrient secretagogues (e.g. D-glucose and L-leucine) act in the B-cell both as substrates and enzyme activators permits reconciliation of the substrate site and regulatory site hypotheses for insulin release.
mesh_terms: D000494:Allosteric Regulation; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007536:Isomerism; D007930:Leucine / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D007328:Insulin; D011956:Receptors, Cell Surface; C027786:glucose receptor; D005969:Glutamate Dehydrogenase; D010732:Phosphofructokinase-1; D011972:Receptor, Insulin; D007930:Leucine; D005947:Glucose