Glutamate inhibits protein phosphatases and promotes insulin exocytosis in pancreatic beta-cells

Biochem Biophys Res Commun. 2005 Mar 11;328(2):601-7. doi: 10.1016/j.bbrc.2005.01.024.

Abstract

In human type 2 diabetes mellitus, loss of glucose-sensitive insulin secretion from the pancreatic beta-cell is an early pathogenetic event, but the mechanisms involved in glucose sensing are poorly understood. A messenger role has been postulated for L-glutamate in linking glucose stimulation to sustained insulin exocytosis in the beta-cell, but the precise nature by which L-glutamate controls insulin secretion remains elusive. Effects of L-glutamate on the activities of ser/thr protein phosphatases (PPase) and Ca(2+)-regulated insulin exocytosis in INS-1E cells were investigated. Glucose increases L-glutamate contents and promotes insulin secretion from INS-1E cells. L-glutamate also dose-dependently inhibits PPase enzyme activities analogous to the specific PPase inhibitor, okadaic acid. L-glutamate and okadaic acid directly and non-additively promote insulin exocytosis from permeabilized INS-1E cells in a Ca(2+)-independent manner. Thus, an increase in phosphorylation state, through inhibition of protein dephosphorylation by glucose-derived L-glutamate, may be a novel regulatory mechanism linking glucose sensing to sustained insulin exocytosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Exocytosis / drug effects
  • Exocytosis / physiology*
  • Glucose / pharmacology*
  • Glutamic Acid / pharmacology*
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphoprotein Phosphatases / metabolism*
  • Rats

Substances

  • Insulin
  • Okadaic Acid
  • Glutamic Acid
  • Phosphoprotein Phosphatases
  • Glucose
  • Calcium