Ng S F, Storlien L H, Kraegen E W, Stuart M C, Chapman G E, Lazarus L
Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia.
Metabolism. 1990 Mar;39(3):264-8. doi: 10.1016/0026-0495(90)90045-e.
Excessive endogenous production or exogenous administration of human growth hormone (hGH) causes insulin resistance at both the hepatic and extrahepatic levels. However, which extrahepatic tissues are involved have not been defined. We have examined the diabetogenic action of authentic biosynthetic hGH on whole body glucose disposal, hepatic glucose output, and glucose metabolism in individual peripheral tissues. The use of a highly purified preparation of the hormone allowed us to examine the isolated effects of 22K hGH. The euglycemic hyperinsulinemic (approximately 100 mU/L) clamp plus 3H-2-deoxyglucose technique was used to quantitate the effects of hGH on insulin action in vivo. Administration of biosynthetic hGH at a dose of 10 IU/kg/24 h for 48 hours in male Wistar rats (approximately 340 g) produced a highly significant decrease in the steady state clamp glucose infusion rate (GIR) when compared with controls (8.1 +/- 0.6 v 18.7 +/- 0.7 mg/kg/min, P less than .001), reduced insulin-mediated suppression of hepatic glucose output (Ra) (3.9 +/- 0.6 v 0.7 +/- 0.3 mg/kg/min, P less than .05) and a decreased clamp glucose disposal rate (Rd) (12.0 +/- 0.4 v 18.10 +/- 1.1 mg/kg/min, P less than .001). There was a significant decrease in insulin-mediated glucose uptake as indicated by tissue accumulation of [3H]-2-deoxyglucose phosphorylation in diaphragm and hindlimb muscles. Insulin action was more substantially reduced in muscles (approximately 50%) than in adipose tissues (approximately 20%). These studies confirm that the diabetogenic action of hGH in the rat is due to a combination of inhibition of insulin suppression of hepatic glucose output and inhibition of the uptake and subsequent utilization of glucose in skeletal muscles.
内源性生长激素（hGH）过度分泌或外源性给予hGH会导致肝脏和肝外组织出现胰岛素抵抗。然而，具体涉及哪些肝外组织尚未明确。我们研究了天然生物合成hGH对全身葡萄糖处置、肝脏葡萄糖输出以及各个外周组织葡萄糖代谢的致糖尿病作用。使用高度纯化的激素制剂使我们能够研究22K hGH的单独作用。采用正常血糖高胰岛素血症（约100 mU/L）钳夹技术加3H-2-脱氧葡萄糖技术来定量hGH对体内胰岛素作用的影响。在雄性Wistar大鼠（约340 g）中，以10 IU/kg/24 h的剂量给予生物合成hGH，持续48小时，与对照组相比，稳态钳夹葡萄糖输注速率（GIR）显著降低（8.1±0.6对18.7±0.7 mg/kg/min，P<0.001），胰岛素介导的肝脏葡萄糖输出抑制作用（Ra）降低（3.9±0.6对0.7±0.3 mg/kg/min，P<0.05），钳夹葡萄糖处置速率（Rd）降低（12.0±0.4对18.10±1.1 mg/kg/min，P<0.001）。膈肌和后肢肌肉中[3H]-2-脱氧葡萄糖磷酸化的组织积累表明，胰岛素介导的葡萄糖摄取显著减少。肌肉中的胰岛素作用比脂肪组织中更显著降低（约50%对约20%）。这些研究证实，hGH在大鼠中的致糖尿病作用是由于抑制胰岛素对肝脏葡萄糖输出的抑制以及抑制骨骼肌对葡萄糖的摄取和后续利用共同作用的结果。
