The molecular mechanisms of insulin secretion and its regulation

Insulin is one of the most important versatile hormone, and its functions include regulation of glycemia homeostasis, enhancement of anabolism, control of cell division and differentiation, modulation of cell growth and development. The molecular mechanisms of insulin release and its regulation can be considered as a paradigm of endocrine secretion. Insulin is stored in large dense core vesicles and released by exocytosis, a multistage process involving transport of vesicles to the membrane, their docking, priming and final fusion with the plasma membrane. SNARE proteins are molecular machinery of exocytosis. Pancreatic islet beta Celts integrate signals of nutrients and hormone/neurotransmitter to release proper quantity of insulin needed for various state. It is well established that glucose and other metabolizable nutrients depotarize the beta cells membrane and ensure Ca2+ influx through the voltage calcium channel by change of ATP/ADP ratio and other metabolic coupling factors. Hormones and neurotransmitters exert their regulation effects on insulin secretion through the signal transduction of heterotrimeric and monomeric G-protein. There are two regulatory steps on exocytosis, proximal regulatory step via the change of second messengers and distal one at the level of exocytosis machinery itself.