Differential Activation Mechanisms of Erk-1/2 and p70S6K by Glucose in Pancreatic β-Cells

• DOI: 10.2337/diabetes.52.4.974
• Publication Date: 2007-03-06T19:04:22Z
• Authors: Isabelle Briaud; Melissa K. Lingohr; Lorna M. Dickson; Christian E. Wrede; Christopher J. Rh...
• Keywords: Male; Mitogen-Activated Protein Kinase 1; 0303 health sciences; Mitogen-Activated Protein Kinase 3; Glucagon-Like Peptides; Glucagon; Isoquinolines; Cyclic AMP-Dependent Protein Kinases; Peptide Fragments; Enzyme Activation; Islets of Langerhans; 03 medical and health sciences; Glucose; Glucagon-Like Peptide 1; Glyburide; Cyclic AMP; Animals; Humans; Calcium; Enzyme Inhibitors; Mitogen-Activated Protein Kinases; Phosphorylation

Glucose can activate the mitogen-activated kinases, Erk-1/2, and ribosomal-S6 kinase, p70S6K, in β-cells, contributing to an increase mitogenesis. However, signaling mechanism by which glucose induces Erk-1/2 p70S6K phosphorylation activation is undefined. Increased metabolism increases [Ca2+]i [cAMP], it was investigated if these secondary signals were linked glucose-induced pancreatic β-cells. Blocking Ca2+ influx with verapamil, or inhibiting protein kinase A (PKA) H89, prevented phosphorylation. Increasing cAMP levels GLP-1 potentiated via PKA activation. Elevation of glyburide phosphorylation, also inhibited suggesting increased preceded for Adenoviral-mediated expression dominant negative Ras INS-1 cells decreased IGF-1-induced but had no effect on that glucose. Collectively, our study indicates a rise leads cAMP-induced acts downstream upstream MAP/Erk MEK, mediate Raf-1. In contrast, activation, same mediated distinct pathway independent Ca2+/cAMP, most likely mTOR-kinase acting as “ATP-sensor.”