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Glucose regulation in adult, male rhesus monkeys: Analysis of intravenous glucose tolerance test data with mathematical modeling.

机译：成年雄性恒河猴的葡萄糖调节：用数学模型分析静脉葡萄糖耐量测试数据。

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摘要

We performed intravenous glucose tolerance tests (IVGTT) under ketamine anesthesia semi-annually or annually for 10 years during a multidimensional study of the effects of aging and adult-onset dietary restriction (DR) in male rhesus monkeys. DR was moderate at ∼30% less that of baseline intake of a semi-purified diet plus daily fruit. Diets of restricted (R) animals were supplemented with a micronutrient mix. Food was available to control (C) animals ad libitum for six to eight hours a day and all animals were individually housed to allow accurate food intake assessment. For the first nine years of the study, we employed Bergman's minimal model to analyze IVGTT data; we estimated indices of insulin sensitivity and glucose effectiveness, which reflect the abilities of insulin and glucose, respectively, to enhance glucose uptake into tissues and to inhibit glucose production. At the 10-year assessment, the animals were middle aged (∼19 yrs); we used glucose tracer data and the minimal models of Cobelli and colleagues to estimate insulin sensitivity and glucose effectiveness related only to glucose uptake. We simultaneously estimated prehepatic insulin secretory parameters. Over time, we found a consistent and profound reduction in fasting plasma insulin, insulin responses to glucose and an enhanced insulin sensitivity among R animals, while among C monkeys we observed low insulin sensitivity and elevated insulin levels. Lower fasting insulin levels were due to lower β-cell sensitivity to glucose among R monkeys and in the dynamic conditions of an IVGTT, the elevated insulin responses of certain obese, hypertriglyceridemic C animals were the result of greater sensitivity suggesting a profile reminiscent of syndrome X described in humans. We also found that body fat was an important mediator, as determined statistically, of the effect we have thus far attributed to DR, suggesting that the mechanism(s) by which DR alters variables of glucose regulation may be related to loss of fat mass. Regardless of its mechanism(s), the available evidence in several species such as rodents, monkeys and the limited studies with humans suggest that DR promotes a healthier physiological profile than does ad libitum caloric intake with increasing age.
机译：我们在氯胺酮麻醉下每半年或每年进行一次静脉葡萄糖耐量试验（IVGTT），为期10年，该试验是对雄性恒河猴衰老和成年饮食限制（DR）影响的多维研究。 DR是中等水平的，比半纯饮食加上每日水果的基线摄入量少约30％。限制动物的饮食中添加了微量营养素混合物。每天有六到八小时可食用食物来控制（C）动物“斜体”（随意），所有动物都单独饲养以进行准确的食物摄入量评估。在研究的前九年中，我们采用了Bergman的最小模型来分析IVGTT数据。我们估计了胰岛素敏感性和葡萄糖有效性的指数，它们分别反映了胰岛素和葡萄糖增强组织摄取葡萄糖和抑制葡萄糖生成的能力。在为期10年的评估中，这些动物为中年（〜19岁）；我们使用葡萄糖示踪剂数据和Cobelli及其同事的最小模型来估计仅与葡萄糖摄取有关的胰岛素敏感性和葡萄糖有效性。我们同时估计了肝前胰岛素分泌参数。随着时间的流逝，我们发现R动物的空腹血浆胰岛素水平持续降低，胰岛素对葡萄糖的反应增强，胰岛素敏感性增强，而C猴中，胰岛素敏感性降低，胰岛素水平升高。空腹胰岛素水平较低是由于R猴子中β细胞对葡萄糖的敏感性较低，并且在IVGTT的动态条件下，某些肥胖，高甘油三酸酯C动物的胰岛素反应升高是其敏感性较高的结果，这暗示了X综合征的特征。在人类中描述。我们还发现，从统计学上确定，人体脂肪是迄今为止我们归因于DR的作用的重要介体，这表明DR改变葡萄糖调节变量的机制可能与脂肪量的减少有关。无论其机制如何，啮齿类动物，猴子和人类有限研究等多种物种的可用证据表明，随着年龄的增长，DR促进的卡路里摄入量比随意摄入的卡路里摄入量更健康。

著录项

  • 作者

    Gresl, Theresa Ann.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Health Sciences Nutrition.; Biology Animal Physiology.; Biology Zoology.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 158 p.
  • 总页数 158
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 预防医学、卫生学;生理学;动物学;
  • 关键词

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