G proteins and modulation of insulin secretion

Guanine nucleotide-binding proteins (G proteins) are critically important mediators of many signaltransduction systems. Several important sites regulating stimulus-secretion coupling and release of insulin from pancreatic β-cells are modulated by G proteins. G_s mediates increases in intracellular cAMP associated with hormone-induced stimulation of insulin secretion. G_l mediates decreases in intracellular cAMP caused by inhibitors of insulin secretion, e.g., epinephrine, somatostatin, prostaglandin E₂, and galanin. G proteins also regulate ion channels, phospholipases, and distal sites in exocytosis. Cholera and pertussis toxins irreversibly ADP ribosylate G proteins and are important tools that can be used both to manipulate G-protein-dependent modulators of insulin secretion and detect and quantify G proteins by electrophoretic techniques. The stage is set to pursue these initial observations in greater depth and ascertain whether G-protein research will provide important new insights into normal and abnormal regulation of insulin secretion.