Cdk5-dependent regulation of glucose-stimulated insulin secretion

摘要: Tight glycemic control in individuals with diabetes mellitus is essential to prevent or delay its complications. Present treatments reduce hyperglycemia mainly target the ATP-sensitive K(+) (K(ATP)) channel of pancreatic beta cells increase insulin secretion. These current approaches are often associated side effect hypoglycemia. Here we show that inhibition activity cyclin-dependent kinase 5 (Cdk5) enhanced secretion under conditions stimulation by high glucose but not low MIN6 and islets. The role Cdk5 regulation was confirmed deficient p35, an activator Cdk5. p35-knockout mice also showed response a challenge. inward whole-cell Ca(2+) increased influx across L-type voltage-dependent (L-VDCC) upon cells, had no on without stimulation. inhibitory L-VDCC attributed phosphorylation loop II-III alpha(1C) subunit at Ser783, which prevented binding SNARE proteins subsequently resulted decrease L-VDCC. results suggest Cdk5/p35 may be drug for glucose-stimulated