Tayek J A
Department of Medicine, Harbor-UCLA Medical Center, Torrance, USA.
J Am Coll Nutr. 1995 Aug;14(4):341-8. doi: 10.1080/07315724.1995.10718519.
Approximately 70% of all cancer patients have elevations in hepatic glucose production and/or reductions in glucose utilization. To identify an explanation for insulin resistance, we measured fasting hepatic glucose production (HGP), leucine appearance (Leu Ra), leucine oxidation (LO), glucose oxidation (GO) and non-oxidative glucose utilization at baseline and after identical insulin infusion rates (2 pmol/kg/minute, 7 pmol/kg/minute, and 70 pmol/kg/minute) in eight head and neck cancer patients and eight weight-matched disease-free volunteers.
A step increase in insulin administration during a euglycemic clamp protocol was used to measure insulin effects on glucose and leucine metabolism. HGP and Leu Ra were determined by performing a primed, continuous 10-hour intravenous infusion of 6-3H glucose and 1-14C leucine. Baseline insulin, thyroid, TNF, and counter-regulatory hormonal measurements, HGP, GO and Leu Ra were obtained between hours 3 and 4. An insulin infusion was started at hour 4 and increased every 2 hours for 6 hours. Glucose appearance, Leu Ra, GO, LO and insulin concentrations were determined at the end of each 2-hour interval.
Fasting HGP, GO, fat oxidation and Leu Ra were similar between the two groups. Insulin administration in cancer patients and normal volunteers had a similar effect on LO and Leu Ra. The insulin concentration required to stimulate half maximal glucose utilization in cancer patients was significantly increased by 58% (470 +/- 82 pM vs. 741 +/- 124 pM; p < or = 0.05). Non-oxidative glucose utilization was reduced in the cancer patients at both lower doses of insulin infusion (6.4 +/- 2.1 mumol/kg/minute vs. 0.1 +/- 1.6 mumol/kg/minute p < or = 0.05; and 23.7 +/- 1.3 mumol/kg/minute vs. 15.1 +/- 2.0 mumol/kg/minute p < 0.01). Triiodothyronine (T3) was directly correlated in the cancer patients with non-oxidative glucose utilization at the two physiological insulin concentrations (r = 0.673, p < 0.05 and r = 0.731, p < 0.01) and the supraphysiological insulin concentration (r = 0.791, p < 0.01). The insulin sensitivity index from the euglycemic clamp study was significantly reduced in the cancer patients (4.7 +/- 0.7 vs. 2.4 +/- 0.1 (dl/min)/(microU/ml); p < 0.05).
In summary, head and neck cancer patients have an abnormal reduction in non-oxidative glucose utilization which occurs before abnormalities in HGP, GO, or Leu Ra [corrected]. One explanation for the reduced glucose utilization may be the influence of a reduced T3 concentration on non-oxidative glucose metabolism but further work is needed to confirm these preliminary observations.
约70%的癌症患者存在肝葡萄糖生成增加和/或葡萄糖利用减少的情况。为了找出胰岛素抵抗的原因，我们在8例头颈癌患者和8例体重匹配的无病志愿者中，测量了基础状态以及在相同胰岛素输注速率（2皮摩尔/千克/分钟、7皮摩尔/千克/分钟和70皮摩尔/千克/分钟）下的空腹肝葡萄糖生成（HGP）、亮氨酸出现率（Leu Ra）、亮氨酸氧化（LO）、葡萄糖氧化（GO）和非氧化葡萄糖利用情况。
在正常血糖钳夹方案中逐步增加胰岛素给药量，以测量胰岛素对葡萄糖和亮氨酸代谢的影响。通过进行6-3H葡萄糖和1-14C亮氨酸的首剂、连续10小时静脉输注来测定HGP和Leu Ra。在第3至4小时期间获取基础胰岛素、甲状腺、肿瘤坏死因子和反调节激素测量值、HGP、GO和Leu Ra。在第4小时开始胰岛素输注，并每2小时增加一次，持续6小时。在每个2小时间隔结束时测定葡萄糖出现率、Leu Ra、GO、LO和胰岛素浓度。
两组之间的空腹HGP、GO、脂肪氧化和Leu Ra相似。癌症患者和正常志愿者中胰岛素给药对LO和Leu Ra有相似的影响。刺激癌症患者半数最大葡萄糖利用所需的胰岛素浓度显著增加了58%（470±82皮摩尔/升对741±124皮摩尔/升；p≤0.05）。在较低剂量胰岛素输注时，癌症患者的非氧化葡萄糖利用减少（6.4±2.1微摩尔/千克/分钟对0.1±1.6微摩尔/千克/分钟，p≤0.05；以及23.7±1.3微摩尔/千克/分钟对15.1±2.0微摩尔/千克/分钟，p＜0.01）。在癌症患者中，三碘甲状腺原氨酸（T3）在两种生理胰岛素浓度（r = 0.673，p＜0.05和r = 0.731，p＜0.01）以及超生理胰岛素浓度（r = 0.791，p＜0.01）下与非氧化葡萄糖利用直接相关。正常血糖钳夹研究中的胰岛素敏感性指数在癌症患者中显著降低（4.7±0.7对2.4±0.1（分升/分钟）/（微单位/毫升）；p＜0.05）。
总之，头颈癌患者在HGP、GO或Leu Ra[校正后]出现异常之前，非氧化葡萄糖利用就已出现异常减少。葡萄糖利用减少的一个原因可能是T3浓度降低对非氧化葡萄糖代谢的影响，但需要进一步研究来证实这些初步观察结果。
