L-Glutamate and insulin enhance glycogen synthesis in cultured astrocytes from the rat brain through different intracellular mechanisms.
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.
Hamai
M
M
Department of Medical Biochemistry, Ehime University School of Medicine, Shigenobu, Japan.
Minokoshi
Y
Y
Shimazu
T
T
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077191:Wortmannin
D000730:Androstadienes; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D001224:Aspartic Acid; D018698:Glutamic Acid; D006003:Glycogen; D003847:Deoxyglucose; D006006:Glycogen Synthase; D005947:Glucose; D000077191:Wortmannin