L-Glutamate and insulin enhance glycogen synthesis in cultured astrocytes from the rat brain through different intracellular mechanisms

J Neurochem. 1999 Jul;73(1):400-7. doi: 10.1046/j.1471-4159.1999.0730400.x.

Abstract

The effects of L-glutamate and insulin on glycogen synthesis in astrocytes were examined. L-Glutamate and insulin both stimulated glycogen synthesis in primary cultures of rat astrocytes in a dose-dependent manner, as measured by the incorporation of 14C from [14C]glucose into glycogen. D-Aspartate also increased the incorporation of 14C into glycogen. When insulin and L-glutamate were added together, the glycogen synthesis as well as glycogen content of the cells was additively increased. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, had little effect on glycogen synthesis induced by L-glutamate, whereas it suppressed the insulin-induced glycogen synthesis. These results suggest that the insulin- and L-glutamate-induced glycogen syntheses are mediated by different intracellular mechanisms. In fact, insulin stimulated the conversion of glycogen synthase b to glycogen synthase a, which was suppressed by wortmannin. L-Glutamate and D-aspartate, however, did not increase the level of glycogen synthase a activity. By contrast, L-glutamate increased 2-deoxy-D-[3H]glucose uptake by the astrocytes, whereas insulin did not affect the uptake. These results suggest that insulin stimulates glycogen synthesis in astrocytes by activating glycogen synthase, which is dependent on a wortmannin-sensitive signaling pathway. L-Glutamate, however, enhances the glucose uptake, which contributes to the increase in glycogen synthesis in the cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Aspartic Acid / pharmacology
  • Astrocytes / drug effects*
  • Astrocytes / metabolism*
  • Brain / cytology*
  • Carbon Radioisotopes
  • Cells, Cultured
  • Deoxyglucose / metabolism
  • Drug Interactions
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Glucose / metabolism
  • Glutamic Acid / pharmacology*
  • Glycogen / biosynthesis*
  • Glycogen Synthase / metabolism
  • Insulin / pharmacology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Wortmannin

Substances

  • Androstadienes
  • Carbon Radioisotopes
  • Enzyme Inhibitors
  • Insulin
  • Phosphoinositide-3 Kinase Inhibitors
  • Aspartic Acid
  • Glutamic Acid
  • Glycogen
  • Deoxyglucose
  • Glycogen Synthase
  • Glucose
  • Wortmannin