Signal mechanism of insulin secretion regulated by bioactive peptides / 中国病理生理杂志

ABSTRACT

Mastoparan(MAS) and α-latrotoxin(α-LTX) are two kinds of insulinotropic peptides obtained from insect toxins which can interact with islet β-cells and induce insulin secretion. The signal mechanism of these insulinotropic peptides regulating insulin-releasing attracts notable attention and has been elucidated more and more details. MAS mainly acts on the molecular components of exocytosis at a late stage. Insulin secretion induced by MAS is obviously dependent on GTP, which subsequently activates G-protein located on insulin secretion granules(ISG), or activates the Rho subfamily of small G proteins to evoke exocytosis and sensitize fusion machinery. The MAS stimulated insulin-releasing activity can be augmented by nutrients. However, its effect is not Ca~(2+) dependent. There are two regulatory pathway triggered by α-LTX one way is pore formation caused through plasma membrane, another way is the transmembrane signal transduction evoked by cytosolic second messengers. Tetrameri complexs assembled at high concentration of α-LTX toxin or in the presence of extracellular Ca~(2+), can insert α-LTX into plasma membrane to form Ca~(2+) permeable channels and trigger Ca~(2+)-dependent secretion. By binding to transmembrane receptors and activating phospholipase C, α-LTX induces the generation of second messenger DAG and IP3. IP3 triggers Ca~(2+) influx and subsequently activates CaMK pathway, however, DAG also activates PKC pathway to increase insulin release.