Biphasic Roles of a Small G-Protein, RAC1 in Pancreatic Β-Cell

Abstract

Glucose-stimulated insulin secretion (GSIS) involves cross talk between small Gproteins
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.