Robinson K A, Willi S M, Bingel S, Buse M G
Division of Endocrinology, Diabetes, and Medical Genetics, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425-2222, USA.
Am J Physiol. 1999 Mar;276(3):E435-42. doi: 10.1152/ajpendo.1999.276.3.E435.
Enhanced glucose flux via the hexosamine biosynthesis pathway (HNSP) has been implicated in insulin resistance. We measured L-glutamine:D-fructose-6-phosphate amidotransferase activity (GFAT, a rate-limiting enzyme) and concentrations of UDP-N-acetyl hexosamines (UDP-HexNAc, major products of HNSP) in muscle and liver of growth hormone (GH)-deficient male dwarf (dw) rats. All parameters measured, except body weight, were similar in 5-wk-old control and dw rats. Muscle GFAT activity declined progressively with age in controls and dw rats but was consistently 30-60% lower in 8- to 14-wk-old dw rats vs. age-matched controls; UDP-HexNAc concentrations in muscle were concomitantly 30% lower in dw rats vs. controls (P < 0.01). Concentrations of UDP-hexoses, GDP-mannose, and UDP in muscle were similar in control and dw rats. Muscle HNSP activity was similarly diminished in fed and fasted dw rats. In liver, only a small difference in GFAT activity was evident between controls and dw rats, and no differences in UDP-HexNAc concentrations were observed. Treatment with recombinant human GH (rhGH) for 5 days restored UDP-HexNAc to control levels in dw muscles (P < 0.01) and partially restored GFAT activity. Insulin-like growth factor I treatment was ineffective. We conclude that GH participates in HNSP regulation in muscle.
通过己糖胺生物合成途径（HNSP）增强的葡萄糖通量与胰岛素抵抗有关。我们测量了生长激素（GH）缺乏的雄性侏儒（dw）大鼠肌肉和肝脏中L-谷氨酰胺：D-果糖-6-磷酸酰胺转移酶活性（GFAT，一种限速酶）以及UDP-N-乙酰己糖胺（UDP-HexNAc，HNSP的主要产物）的浓度。除体重外，所有测量参数在5周龄的对照大鼠和dw大鼠中相似。在对照大鼠和dw大鼠中，肌肉GFAT活性均随年龄逐渐下降，但在8至14周龄的dw大鼠中，其活性始终比年龄匹配的对照大鼠低30-60%；dw大鼠肌肉中的UDP-HexNAc浓度比对照大鼠低30%（P < 0.01）。对照大鼠和dw大鼠肌肉中的UDP-己糖、GDP-甘露糖和UDP浓度相似。喂食和禁食的dw大鼠肌肉中的HNSP活性同样降低。在肝脏中，对照大鼠和dw大鼠之间仅在GFAT活性上有微小差异，且未观察到UDP-HexNAc浓度有差异。用重组人生长激素（rhGH）治疗5天可使dw大鼠肌肉中的UDP-HexNAc恢复到对照水平（P < 0.01），并部分恢复GFAT活性。胰岛素样生长因子I治疗无效。我们得出结论，生长激素参与肌肉中HNSP的调节。
