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

H. Yki-Järvinen, C. Vogt, P. Iozzo, R. Pipek, M. C. Daniels, A. Virkamäki, S. Mäkimattila, L. Mandarino, R. A. DeFronzo, D. McClain, W. K. Gottschalk

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Glutamine:fructose 6-phosphate amidotransferase (GFA) is rate-limiting for hexosamine biosynthesis, while a UDP-GlcNAc β-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.

Original languageEnglish (US)
Pages (from-to)76-81
Number of pages6
JournalDiabetologia
Volume40
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

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Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Insulin
Skeletal Muscle
Type 2 Diabetes Mellitus
Hexosamines
Uridine Diphosphate
Hyperinsulinism
Threonine
Glycosylation
Serine
UDP-N-acetylglucosamine transferase
O-GlcNAc transferase
Glucose
Submandibular Gland
Liver
Intravenous Infusions
Human Activities
Insulin Resistance
High Pressure Liquid Chromatography

Keywords

  • diabetes mellitus
  • glucose
  • hexosamines
  • insulin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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

UDP-N-acetylglucosamine transferase and glutamine : Fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. / Yki-Järvinen, H.; Vogt, C.; Iozzo, P.; Pipek, R.; Daniels, M. C.; Virkamäki, A.; Mäkimattila, S.; Mandarino, L.; DeFronzo, R. A.; McClain, D.; Gottschalk, W. K.

In: Diabetologia, Vol. 40, No. 1, 1997, p. 76-81.

Research output: Contribution to journalArticle

Yki-Järvinen, H, Vogt, C, Iozzo, P, Pipek, R, Daniels, MC, Virkamäki, A, Mäkimattila, S, Mandarino, L, DeFronzo, RA, McClain, D & Gottschalk, WK 1997, 'UDP-N-acetylglucosamine transferase and glutamine: Fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues', Diabetologia, vol. 40, no. 1, pp. 76-81. https://doi.org/10.1007/s001250050645
Yki-Järvinen, H. ; Vogt, C. ; Iozzo, P. ; Pipek, R. ; Daniels, M. C. ; Virkamäki, A. ; Mäkimattila, S. ; Mandarino, L. ; DeFronzo, R. A. ; McClain, D. ; Gottschalk, W. K. / UDP-N-acetylglucosamine transferase and glutamine : Fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. In: Diabetologia. 1997 ; Vol. 40, No. 1. pp. 76-81.
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AU - Pipek, R.

AU - Daniels, M. C.

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