title: Rapid activation and nuclear translocation of mitogen-activated protein kinases in response to physiological concentration of glucose in the MIN6 pancreatic beta cell line.
abstract: MIN6 is one of the few pancreatic beta cell lines that respond to physiological concentrations of glucose by secreting insulin, and little is known about the triggered molecular mechanisms. We report below that the response to glucose in the MIN6 cells includes an activation of the p42 and p44 mitogen-activated protein (MAP) kinases (ERK2 and ERK1). This activation also occurred with the antidiabetic sulfonylurea glibenclamide and kainate, a specific agonist of a subtype of the ionotropic glutamate receptors, which depolarize the cytoplasmic membrane. The requirement for a calcium entry through the L-type voltage-gated channels and other characteristics of the regulation of the MAP kinase activity, such as the effect of the elevation of the cAMP concentration by forskolin, were similar to those of the secretion of insulin. However, the activation of the MAP kinases is not required for the secretion of insulin, inasmuch as this effect of glucose was not abolished when the MAP kinases were prevented from activation by PD098059, an inhibitor of the MAP kinase kinase. However, as the MAP kinases were translocated into the nucleus, they might be implicated in the calcium-dependent transcriptional response of the cells to glucose and thus regulate the expression of the insulin gene.
authors.affiliation: Laboratoire Signalisation Cellulaire et Parasites, UFR Cochin Université René Descartes, Pavillon Gustave Roussy (6ème étage), 27, rue du Faubourg Saint Jacques, 75674 Paris cedex 14, France.
authors.forename: C
authors.initials: C
authors.lastname: Benes
authors.forename: M P
authors.initials: MP
authors.lastname: Roisin
authors.forename: H
authors.initials: H
authors.lastname: Van Tan
authors.forename: C
authors.initials: C
authors.lastname: Creuzet
authors.forename: J
authors.initials: J
authors.lastname: Miyazaki
authors.forename: R
authors.initials: R
authors.lastname: Fagard
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D005947:Glucose / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D007608:Kainic Acid / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D017470:Receptors, Glutamate; D005576:Colforsin; D004533:Egtazic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009543:Nifedipine; D005947:Glucose; D011188:Potassium; D007608:Kainic Acid; D005905:Glyburide; D002118:Calcium