Insulin and glucosamine infusions increase O-linked N-acetyl-glucosamine in skeletal muscle proteins in vivo

• Published in: Metabolism, clinical and experimental Vol. 47; no. 4; pp. 449 - 455
• Main Authors: Yki-Järvinen, Hannele, Virkamäki, Antti, Daniels, Marc C., McClain, Don, Gottschalk, W.Kirby
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.1998; Elsevier
• Subjects: Acetylglucosamine - metabolism; Animals; Biological and medical sciences; Blood Glucose - metabolism; Carbohydrate Conformation; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Glucosamine - analogs & derivatives; Glucosamine - blood; Glucosamine - pharmacology; Glycolysis - physiology; Hormones. Régulation; Infusions, Intravenous; Infusions, Parenteral; Insulin - blood; Insulin - pharmacology; Male; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Rats; Rats, Wistar; Uridine Diphosphate Galactose - blood; Vertebrates: endocrinology; Pancreatic hormone; Glucosamine; Rat; Threonine; Metabolite; Cell nucleus; Serine; Rodentia; Striated muscle; Insulin; Protein; Protein hormone; In vivo; Vertebrata; Mammalia; Aminoacid; Animal; Biological effect; Cytoplasm
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(98)90058-0

O-linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification of serine/threonine residues of nuclear and cytoplasmic proteins. We determined whether insulin or coinfusion of glucosamine (GlcN) with insulin alters O-GlcNAc of skeletal muscle proteins. Three groups of conscious fasted rats received 6-hour infusions of either saline (BAS), insulin 18 mU/kg · min and saline (INS), or insulin and GlcN 30 μmol/kg · min (GLCN) during maintenance of normoglycemia. At 6 hours, the concentrations of muscle UDP-GlcNAc, UDP- N-acetylgalactosamine (UDP-GalNAc), UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal), glycogen, and N- and O-linked GlcNAc (galactosyltransferase labeling followed by β elimination) were measured in freeze-clamped abdominis muscle. Insulin increased whole-body glucose uptake from 49 ± 5 to 239 ± 8 μmol/kg · min ( P < .001) and glycogen in abdominis muscle from 138 ± 11 to 370 ± 26 mmol/kg dry weight ( P < .001). Insulin increased the amount of cytosolic N- and O-linked GlcNAc by 56% from 362 ± 30 to 564 ± 45 dpm/μg protein · 100 min ( P < .02), and O-GlcNAc from 221 ± 16 to 339 ± 27 dpm/μg · 100 min ( P < .02). Glycogen content was positively correlated with the amount of total ( r = .90, P < .005) and O-linked GlcNAc in insulin-infused animals. Coinfusion of GlcN with insulin increased muscle UDP-GlcNAc about fourfold (100 ± 6 nmol/g) compared with insulin (27 ± 1, P < .001) or saline (25 ± 1, P < .001) infusion. GlcN also decreased glucose uptake over 6 hours by 30% to 168 ± 8 μmol/kg · min ( P < .001 for GLCN v INS) and muscle glycogen to 292 ± 24 mmol/kg dry weight ( P < .05 for GLCN v INS). Both total (635 ± 60 dpm/μg · 100 min, P < .002) and O -linked GlcNAc (375 ± 36 dpm/μg · 100 min, P < .002) in the cytosol were significantly higher in GLCN rats (635 ± 60 dpm/μg) versus BAS rats ( P < .002). As in INS rats, muscle glycogen and O-GlcNAc were positively correlated in GLCN rats ( r = .54, P < .05). Variation in total and O-linked GlcNAc in GLCN rats was due both to GlcN ( P < .02) and to variation in the glycogen content ( P < .005).