INSULIN EFFECTS ON INTRAMUSCULAR FATTY ACID METABOLISM

胰岛素对肌内脂肪酸代谢的影响

• 批准号: 6264998
• 负责人: M D JENSEN
• 金额: $ 2.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264998
• 关键词: clinical research; fatty acid metabolism; hormone regulation /control mechanism; human subject; insulin; insulin sensitivity /resistance; muscle metabolism; obesity; striated muscles

Intramuscular TFGA are 2-4 fold greater in insulin resistant, obese than in lean, insulin sensitive humans. These enlarged lipid stores are proposed to contribute to skeletal muscle insulin resistance vi the glucose fatty acid cycle. Endurance trained humans also have increased intramuscular TGFA, however, and are not insulin resistant. If intramusclar FA contibute to insulin resistance, intramuscular TGFA kinetics must be regulated quite differently in these two groups. The differences could be present under basal conditions in response to insulin or both. We anticipate that basal intramuscular TGFA hydrolysis will be increased in visceral obesity in proportion to the increased TGFA stores, and that hydrolysis rates will not be inhibited by insulin in this group. The results will provide the first available information regarding the kinetics of intramuscular FA in humans and will help us to understand the role of this small, but potentially important lipid pool in the syndrome of insulin resistance/visceral obesity. Early analysis of samples obtained from the first few studies revealed inadequate stable isotope incorporation into the muscle biopsy specimens. Therefore, a protocol change was made increasing the doses of the stable fatty acids and adding radioisotopes of the same fatty acids. To offset the increase in radiation exposure, the 3H-glucose was changed to stable 2H-glucose (IRB and radiation safety approval 10/2 and 9/29 respectively).

在胰岛素抵抗、肥胖的人中，肌内TFGA是瘦的、胰岛素敏感的人中的2-4倍。 这些扩大的脂质储存被认为是通过葡萄糖脂肪酸循环导致骨骼肌胰岛素抵抗的原因。 然而，耐力训练的人也增加了肌内TGFA，并且没有胰岛素抵抗。 如果肌内脂肪酸与胰岛素抵抗有关，那么肌内TGFA动力学在这两组中的调节方式肯定是完全不同的。 基础状态下对胰岛素或两者的反应可能存在差异。 我们预计，基础肌内TGFA水解将增加内脏肥胖的比例增加TGFA存储，水解率不会被胰岛素抑制在这一组。 结果将提供第一个可用的信息，肌肉内脂肪酸在人类的动力学，并将帮助我们了解这个小的，但潜在的重要脂质池中的胰岛素抵抗/内脏肥胖综合征的作用。对最初几项研究中获得的样本进行的早期分析显示，肌肉活检标本中的稳定同位素掺入不足。因此，对方案进行了变更，增加了稳定脂肪酸的剂量，并添加了相同脂肪酸的放射性同位素。 为了抵消辐射暴露的增加，将3 H-葡萄糖变更为稳定的2 H-葡萄糖（IRB和辐射安全批准分别为10/2和9/29）。