Phospho-serine/threonine phosphatases in rat islets of Langerhans: identification and effect on insulin secretion.

Stimulation of insulin secretion is accompanied by changes in the phosphorylation state of several islet polypeptides. Protein (de)phosphorylation is mediated by the action of protein kinases and phosphoprotein phosphatases. In this study we have investigated expression of phospho-serine/threonine phosphatases (PPs) in rat islets of Langerhans and studied the role of these enzymes in the regulation of insulin secretion. PP1, PP2A and PP2B were identified in rat islets and high levels of PP1/2A activities were detected. Inhibition of PP1/2A markedly inhibited glucose-stimulated insulin secretion, whilst glucose increased islet PP1/2A activities in situ. Insulin secretion at basal glucose was unaffected by inhibitors of PP1/2A. Inhibition of PP2B had no effect on either basal or glucose stimulated insulin secretion. These results suggest that PP1/2A are stimulated by glucose in rat islets and the presence of active PP1/2A is required for stimulation of insulin secretion by glucose.