Malaisse W J, Sener A, Malaisse-Lagae F
Mol Cell Biochem. 1981 Jul;37(3):157-65. doi: 10.1007/BF02354884.
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.
目前认为，刺激胰岛素分泌的营养物质最终导致胰岛素释放，这一系列细胞事件的起始，要么是通过与立体特异性受体系统相互作用（调节位点假说），要么是在胰腺β细胞中作为燃料起作用（底物位点假说）。后一种假说得到了一些观察结果的支持，这些观察结果表明，营养物质刺激胰岛素释放的能力确实高度依赖于它们在分离的胰岛中增加分解代谢通量的能力。然而，这些观察结果并不排除胰岛细胞中存在营养物质受体。例如，L-亮氨酸的一种非代谢类似物通过引起谷氨酸脱氢酶的变构激活来刺激胰岛素释放，因此，应该将其视为某些氨基酸的受体。同样，与葡萄糖刺激胰岛素释放过程相关的糖酵解通量增加，不仅归因于质量作用现象，还归因于果糖2,6-二磷酸对磷酸果糖激酶的激活。这种激活剂的生物合成可能涉及葡萄糖受体系统。某些营养促分泌剂（如D-葡萄糖和L-亮氨酸）在β细胞中既作为底物又作为酶激活剂起作用，这一事实使得胰岛素释放的底物位点假说和调节位点假说能够统一起来。
