PMID: 8593937Mar 1, 1996Paper

Regulation of glycogen synthase and protein phosphatase-1 by hexosamines

Diabetes
E D Crook, D McClain

Abstract

The hexosamine biosynthesis pathway has been hypothesized to be involved in mediating some of the adverse effects of high glucose. We have previously shown that glucose downregulates basal glycogen synthase (GS) activity in Rat-1 cells and that overexpressing the rate-limiting enzyme in the hexosamine biosynthesis pathway (glutamine:fructose-6-phosphate amidotransferase [GFA]) makes the cells more sensitive to these effects of glucose. GFA overexpression also leads to a reduction in insulin sensitivity of GS. Here we examine the effects of glucose and glucosamine on insulin-stimulated GS activity and on protein phosphatase-1 (PP1) activity. These activities were assayed in cytoplasmic extracts from Rat-1 fibroblasts overexpressing human GFA and cultured in varying glucose concentrations. Both maximal insulin-stimulated GS activity and insulin sensitivity decreased with increasing glucose. Overexpression of GFA leads to a further reduction in insulin sensitivity but not in maximal insulin-stimulated GS activity. Because there were no differences in total (glucose-6-phosphate-dependent) GS activity between cell lines or as a function of glucose concentration, these results most likely reflect a change in the phosphorylation state...Continue Reading

Citations

Jun 5, 2002·Biochimica Et Biophysica Acta·Sławomir Milewski
Mar 16, 2004·Pediatric Diabetes·Eva GyürüsUNKNOWN Hungarian Childhood Diabetes Epidemiology Study Group
May 1, 1997·The American Journal of Physiology·B A NelsonM G Buse
Jan 3, 2003·The Journal of Biological Chemistry·Glendon J ParkerDonald A McClain
Sep 29, 2005·American Journal of Physiology. Endocrinology and Metabolism·Robert C CookseyDonald A McClain
Jun 6, 2017·Endocrinology·Sarah E Hugo, Amnon Schlegel
Aug 1, 1998·The Journal of Biological Chemistry·R C HreskoM Mueckler
Feb 13, 1997·Biochemical and Biophysical Research Communications·R S HaltiwangerR Scartozzi

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