Biphasic Roles of a Small G-Protein, RAC1 in Pancreatic Β-Cell
DOI:
https://doi.org/10.17140/GOJ-1-114Keywords:
Small G-protein, Rac, Insulin secretion, NADPH oxidase, Oxidative stress, IsletsAbstract
Glucose-stimulated insulin secretion (GSIS) involves cross talk between small G proteins and their regulating factors. These interactions results in translocation of insulin-laden granules to the plasma membrane for fusion and insulin release. Vesicular transport and fusion events are tightly regulated by signals which coordinate between vesicle- and membrane-associated docking proteins. It is now being accepted that small G-protein, Rac1-mediated Reactive Oxygen Species (ROS) functions as a second messenger in islet β-cell function. Further, evidence from multiple laboratories suggests a tonic increase in ROS generation is necessary for GSIS and fatty acid-induced insulin secretion. On the other hand, Rac1-mediated NADPH oxidase-activation and subsequent generation of excessive ROS under glucolipotoxic conditions and cytokines exposure has proven to be detrimental for islet β-cell function. In this review we overview the normal physiological effects (positive role) and adverse effects (negative role) of activated small G-protein, Rac1 in pancreatic β-cells.
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