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L‐Glutamate and Insulin Enhance Glycogen Synthesis in Cultured Astrocytes from the Rat Brain Through Different Intracellular Mechanisms
Author(s) -
Hamai Meiko,
Minokoshi Yasuhiko,
Shimazu Takashi
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730400.x
Subject(s) - glycogen synthase , glycogen , wortmannin , glycogen branching enzyme , glycogenesis , glycogen phosphorylase , glutamate receptor , insulin , medicine , endocrinology , biology , astrocyte , gsk 3 , biochemistry , chemistry , phosphatidylinositol , kinase , receptor , central nervous system
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 14 C from [ 14 C]glucose into glycogen. D‐Aspartate also increased the incorporation of 14 C 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‐[ 3 H]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.