Glutamine:fructose-6-phosphate amidotransferase activity in cultured human skeletal muscle cells: relationship to glucose disposal rate in control and non-insulin-dependent diabetes mellitus subjects and regulation by glucose and insulin. (original) (raw)
- Journal List
- J Clin Invest
- v.97(5); 1996 Mar 1
- PMC507176
J Clin Invest. 1996 Mar 1; 97(5): 1235–1241.
Veterans Administration Medical Center, University of Mississippi Medical Center, Jackson 39216, USA.
Abstract
We examined the activity of the rate-limiting enzyme for hexosamine biosynthesis, glutamine:fructose-6-phosphate amidotransferase (GFA) in human skeletal muscle cultures (HSMC), from 17 nondiabetic control and 13 subjects with non-insulin-dependent diabetes. GFA activity was assayed from HSMC treated with low (5 mM) or high (20 mM) glucose and low (22 pM) or high (30 microM) concentrations of insulin. In control subjects GFA activity decreased with increasing glucose disposal rate (r = -0.68, P < 0.025). In contrast, a positive correlation existed between GFA and glucose disposal in the diabetics (r = 0.86, P < 0.005). Increased GFA activity was also correlated with body mass index in controls but not diabetics. GFA activity was significantly stimulated by high glucose (22%), high insulin (43%), and their combination (61%). GFA activity and its regulation by glucose and insulin were not significantly different in diabetic HSMC. We conclude that glucose and insulin regulate GFA activity in skeletal muscle. More importantly, our results are consistent with a regulatory role for the hexosamine pathway in human glucose homeostasis. This relationship between hexosamine biosynthesis and the regulation of glucose metabolism is altered in non-insulin-dependent diabetes.
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- Yki-Järvinen H. Glucose toxicity. Endocr Rev. 1992 Aug;13(3):415–431. [PubMed] [Google Scholar]
- Unger RH. Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells. Science. 1991 Mar 8;251(4998):1200–1205. [PubMed] [Google Scholar]
- Marshall S, Bacote V, Traxinger RR. Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem. 1991 Mar 15;266(8):4706–4712. [PubMed] [Google Scholar]
- Daniels MC, Kansal P, Smith TM, Paterson AJ, Kudlow JE, McClain DA. Glucose regulation of transforming growth factor-alpha expression is mediated by products of the hexosamine biosynthesis pathway. Mol Endocrinol. 1993 Aug;7(8):1041–1048. [PubMed] [Google Scholar]
- McClain DA, Paterson AJ, Roos MD, Wei X, Kudlow JE. Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8150–8154. [PMC free article] [PubMed] [Google Scholar]
- Crook ED, Daniels MC, Smith TM, McClain DA. Regulation of insulin-stimulated glycogen synthase activity by overexpression of glutamine: fructose-6-phosphate amidotransferase in rat-1 fibroblasts. Diabetes. 1993 Sep;42(9):1289–1296. [PubMed] [Google Scholar]
- Crook ED, Zhou J, Daniels M, Neidigh JL, McClain DA. Regulation of glycogen synthase by glucose, glucosamine, and glutamine:fructose-6-phosphate amidotransferase. Diabetes. 1995 Mar;44(3):314–320. [PubMed] [Google Scholar]
- Robinson KA, Sens DA, Buse MG. Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor. Diabetes. 1993 Sep;42(9):1333–1346. [PubMed] [Google Scholar]
- Balkan B, Dunning BE. Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats. Diabetes. 1994 Oct;43(10):1173–1179. [PubMed] [Google Scholar]
- Traxinger RR, Marshall S. Insulin regulation of pyruvate kinase activity in isolated adipocytes. Crucial role of glucose and the hexosamine biosynthesis pathway in the expression of insulin action. J Biol Chem. 1992 May 15;267(14):9718–9723. [PubMed] [Google Scholar]
- Traxinger RR, Marshall S. Coordinated regulation of glutamine:fructose-6-phosphate amidotransferase activity by insulin, glucose, and glutamine. Role of hexosamine biosynthesis in enzyme regulation. J Biol Chem. 1991 Jun 5;266(16):10148–10154. [PubMed] [Google Scholar]
- McKnight GL, Mudri SL, Mathewes SL, Traxinger RR, Marshall S, Sheppard PO, O'Hara PJ. Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase. J Biol Chem. 1992 Dec 15;267(35):25208–25212. [PubMed] [Google Scholar]
- Zhou J, Neidigh JL, Espinosa R, 3rd, LeBeau MM, McClain DA. Human glutamine: fructose-6-phosphate amidotransferase: characterization of mRNA and chromosomal assignment to 2p13. Hum Genet. 1995 Jul;96(1):99–101. [PubMed] [Google Scholar]
- Henry RR, Abrams L, Nikoulina S, Ciaraldi TP. Insulin action and glucose metabolism in nondiabetic control and NIDDM subjects. Comparison using human skeletal muscle cell cultures. Diabetes. 1995 Aug;44(8):936–946. [PubMed] [Google Scholar]
- Ciaraldi TP, Abrams L, Nikoulina S, Mudaliar S, Henry RR. Glucose transport in cultured human skeletal muscle cells. Regulation by insulin and glucose in nondiabetic and non-insulin-dependent diabetes mellitus subjects. J Clin Invest. 1995 Dec;96(6):2820–2827. [PMC free article] [PubMed] [Google Scholar]
- Thorburn AW, Gumbiner B, Bulacan F, Wallace P, Henry RR. Intracellular glucose oxidation and glycogen synthase activity are reduced in non-insulin-dependent (type II) diabetes independent of impaired glucose uptake. J Clin Invest. 1990 Feb;85(2):522–529. [PMC free article] [PubMed] [Google Scholar]
- Mueckler M. Facilitative glucose transporters. Eur J Biochem. 1994 Feb 1;219(3):713–725. [PubMed] [Google Scholar]
- Sarabia V, Ramlal T, Klip A. Glucose uptake in human and animal muscle cells in culture. Biochem Cell Biol. 1990 Feb;68(2):536–542. [PubMed] [Google Scholar]
- Adler AJ. Glutamine fructose-6-phosphate aminotransferase and glycoprotein synthesis in the developing chick eye. Curr Eye Res. 1984 Feb;3(2):351–362. [PubMed] [Google Scholar]
- Richards TC, Greengard O. Distribution of glutamine hexosephosphate aminotransferase in rat tissues; changes with state of differentiation. Biochim Biophys Acta. 1973 May 28;304(3):842–850. [PubMed] [Google Scholar]
- Tsuiki S, Miyagi T. Neoplastic alterations of glucosamine 6-phosphate synthase in rat liver. Adv Enzyme Regul. 1976;15:35–52. [PubMed] [Google Scholar]
- Winterburn PJ, Phelps CF. Purification and some kinetic properties of rat liver glucosamine synthetase. Biochem J. 1971 Feb;121(4):701–709. [PMC free article] [PubMed] [Google Scholar]
- Kornfeld R. Studies on L-glutamine D-fructose 6-phosphate amidotransferase. I. Feedback inhibition by uridine diphosphate-N-acetylglucosamine. J Biol Chem. 1967 Jul 10;242(13):3135–3141. [PubMed] [Google Scholar]
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