EFFECT OF DIETARY RESTRICTION & AGING ON GLUCOSE REGULATION

目的确定饮食限制对 胰岛素和葡萄糖代谢在老龄猕猴与使用 静脉葡萄糖耐量试验（FSIGT）。 第二，进行小型试验研究，探讨 进行放射性标记的正常血糖高胰岛素钳夹程序 在饮食限制和随意喂养的老龄猴中。 结果 68只雄性和雌性恒河猴在三个实验中 作为正在进行的多维研究的一部分， 衰老和饮食限制的影响。 一半的动物 在每一组中， 饮食，已被能量限制了20- 30%。 限制性（R）比较 自1989年以来研究的第1组中自由采食对照（C）猴 空腹血糖和胰岛素水平较低， 反应，以及更高的胰岛素敏感性指数， FSIGT半年度数据的最小模型分析。 类似的结果 在R和C猴之间，在较年轻的2组雄性中观察到， 第3组女性自1994年起接受研究。 一项小型试点研究也 用一个单独的8只恒河猴组进行， 放射性标记的正葡萄糖高胰岛素钳夹程序，以确定 稳态肝脏葡萄糖生成，以及肝脏和外周 胰岛素敏感性未来的方向我们打算继续执行 这三个组每年进行一次FSIGT程序。 我们将 还扩展了FSIGT协议，以包括使用稳定标记的 葡萄糖同位素，其虽然基本上不改变电流 协议，将使我们能够模拟胰岛素和C肽数据， 测定肝葡萄糖生成。 关键词饮食限制; 衰老;糖代谢;胰岛素敏感性基金NIH P01 AG 11915 Gresl，T.，Roecker，E.，哈维赫斯特，T.，Baum，S.，和 Kemnitz，J.慢性饮食限制可防止胰岛素 抵抗和2型糖尿病在成年恒河猴。 糖尿病 47（补编1）A310，1998年。 Gresl，T.，Cartee，G.，Gazdag，A.，洛克， E、科尔曼河，Baum，S.，梅森湖，Kemnitz，J. Dietary 2型糖尿病的发病机制 恒河猴 FASEB Journal 12（4）A254，1998.

OBJECTIVE To determine the effect of dietary restriction on insulin and glucose metabolism in aging macaques with the use of frequently sampled intravenous glucose tolerance tests (FSIGT). Secondly, to perform a small pilot study on the feasibility of conducting radiolabeled euglycemic hyperinsulinemic clamp procedures in dietary restricted and ad libitum-fed aging monkeys. RESULTS Sixty-eight male and female rhesus macaques in three experimental groups were studied as part of an ongoing multidimensional study of the effects of aging and dietary restriction. One half of the animals in each group, with adequate supplemental micronutrients in their diets, have been energy restricted by 20-30%. Restricted (R) compared to ad libitum-fed control (C) monkeys in group 1 studied since 1989 exhibited lower fasting glucose and insulin levels, lower insulin responses, and higher insulin sensitivity indices as determined from minimal model analysis of the semi-annual FSIGT data. Similar results are seen between R and C monkeys in the younger group 2 males and group 3 females studied since 1994. A small pilot study was also conducted with a separate group of eight rhesus macaques using a radio-labeled euglycemic hyperinsulinemic clamp procedure to determine steady state hepatic glucose production, and hepatic and peripheral insulin sensitivity FUTURE DIRECTIONS We intend to continue to perform FSIGT procedures on an annual basis in these three groups. We will also expand the FSIGT protocol to include the use of a stable-labeled glucose isotope, which, while not substantially altering the current protocol, will enable us to model insulin and C-peptide data, and to determine hepatic glucose production. KEY WORDS dietary restriction; aging; glucose metabolism; insulin sensitivity FUNDING NIH P01 AG11915 PUBLICATIONS Gresl, T., Roecker, E., Havighurst, T., Baum, S., and Kemnitz, J. Chronic dietary restriction protects against insulin resistance and type 2 diabetes in adult rhesus monkeys. Diabetes 47(Suppl. 1) A310, 1998. Gresl, T., Cartee, G., Gazdag, A., Roecker, E., Colman, R., Baum, S., Mason, L., and Kemnitz, J. Dietary restriction protects against the development of type 2 diabetes in rhesus monkeys. FASEB Journal 12(4) A254 , 1998.