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UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues.

Publication ,  Journal Article
Yki-Järvinen, H; Vogt, C; Iozzo, P; Pipek, R; Daniels, MC; Virkamäki, A; Mäkimattila, S; Mandarino, L; DeFronzo, RA; McClain, D; Gottschalk, WK
Published in: Diabetologia
January 1997

Glutamine:fructose 6-phosphate amidotransferase (GFA) is rate-limiting for hexosamine biosynthesis, while a UDP-GlcNAc beta-N-acetylglucosaminyltransferase (O-GlcNAc transferase) catalyses final O-linked attachment of GlcNAc to serine and threonine residues on intracellular proteins. Increased activity of the hexosamine pathway is a putative mediator of glucose-induced insulin resistance but the mechanisms are unclear. We determined whether O-GlcNAc transferase is found in insulin-sensitive tissues and compared its activity to that of GFA in rat tissues. We also determined whether non-insulin-dependent diabetes mellitus (NIDDM) or acute hyperinsulinaemia alters O-GlcNAc transferase activity in human skeletal muscle. O-GlcNAc transferase was measured using 3H-UDP-GlcNAc and a synthetic cationic peptide substrate containing serine and threonine residues, and GFA was determined by measuring a fluorescent derivative of GlcN6P by HPLC. O-GlcNAc transferase activities were 2-4 fold higher in skeletal muscles and the heart than in the liver, which had the lowest activity, while GFA activity was 14-36-fold higher in submandibular gland and 5-18 fold higher in the liver than in skeletal muscles or the heart. In patients with NIDDM (n = 11), basal O-GlcNAc transferase in skeletal muscle averaged 3.8 +/- 0.3 nmol/mg.min, which was not different from that in normal subjects (3.3 +/- 0.4 nmol/mg.min). A 180-min intravenous insulin infusion (40 mU/m2.min) did not change muscle O-GlcNAc transferase activity in either group. We conclude that O-GlcNAc transferase is widely distributed in insulin-sensitive tissues in the rat and is also found in human skeletal muscle. These findings suggest the possibility that O-linked glycosylation of intracellular proteins is involved in mediating glucose toxicity. O-GlcNAc transferase does not, however, appear to be regulated by either NIDDM or acute hyperinsulinaemia, suggesting that mass action effects determine the extent of O-linked glycosylation under hyperglycaemic conditions.

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Published In

Diabetologia

DOI

EISSN

1432-0428

ISSN

0012-186X

Publication Date

January 1997

Volume

40

Issue

1

Start / End Page

76 / 81

Related Subject Headings

  • Submandibular Gland
  • Sensitivity and Specificity
  • Rats, Sprague-Dawley
  • Rats
  • N-Acetylglucosaminyltransferases
  • Myocardium
  • Muscle, Skeletal
  • Male
  • Liver
  • Insulin Resistance
 

Citation

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Yki-Järvinen, H., Vogt, C., Iozzo, P., Pipek, R., Daniels, M. C., Virkamäki, A., … Gottschalk, W. K. (1997). UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. Diabetologia, 40(1), 76–81. https://doi.org/10.1007/s001250050645
Yki-Järvinen, H., C. Vogt, P. Iozzo, R. Pipek, M. C. Daniels, A. Virkamäki, S. Mäkimattila, et al. “UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues.Diabetologia 40, no. 1 (January 1997): 76–81. https://doi.org/10.1007/s001250050645.
Yki-Järvinen H, Vogt C, Iozzo P, Pipek R, Daniels MC, Virkamäki A, et al. UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. Diabetologia. 1997 Jan;40(1):76–81.
Yki-Järvinen, H., et al. “UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues.Diabetologia, vol. 40, no. 1, Jan. 1997, pp. 76–81. Epmc, doi:10.1007/s001250050645.
Yki-Järvinen H, Vogt C, Iozzo P, Pipek R, Daniels MC, Virkamäki A, Mäkimattila S, Mandarino L, DeFronzo RA, McClain D, Gottschalk WK. UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. Diabetologia. 1997 Jan;40(1):76–81.
Journal cover image

Published In

Diabetologia

DOI

EISSN

1432-0428

ISSN

0012-186X

Publication Date

January 1997

Volume

40

Issue

1

Start / End Page

76 / 81

Related Subject Headings

  • Submandibular Gland
  • Sensitivity and Specificity
  • Rats, Sprague-Dawley
  • Rats
  • N-Acetylglucosaminyltransferases
  • Myocardium
  • Muscle, Skeletal
  • Male
  • Liver
  • Insulin Resistance