IN VIVO 23NA NMR SPECTROSCOPY & IMAGING

Zucker糖尿病肥胖大鼠是一种公认的人类糖尿病模型。 肥胖和NIDDM。 遗传瘦素受体缺陷的动物 (fa/fa）发展为早期肥胖胰岛素抵抗，男性发展为NIDDM 因为他们的瘦素抵抗。 我们已经证明，光谱 全身脂肪含量分析检测肥胖前期（fa/fa） 严重肥胖和其他代谢紊乱前的基因型 开发. 此外，该分析还提供了一种衡量瘦体的方法， 质量使用我们以前的验证技术的脂肪和全身 水检测 我们发现这个动物模型 同时存在的瘦体重积累缺陷。 偶然地， 第二个模型使用i. c. v.瘦素输注到正常大鼠中，我们 观察到除了增加脂肪外， 由瘦素的中枢作用介导的氧化。 高胰岛素 在这两种动物模型中的葡萄糖钳夹研究表明， 肌细胞内甘油三酯含量与 胰岛素敏感性 我们已经能够具体监测到 通过使用质子光谱法测定肌细胞内脂质， 之前已经使用1.5T验证了其在犬和兔中的使用 罗杰斯MR中心的临床MR系统。 研究目前在 在更好地了解数额与 膳食脂肪类型，瘦素，瘦素抵抗，肌细胞内 甘油三酯储存和胰岛素抵抗的发展， 胰岛素分泌反应受损。 （服务5）报告期： (09（1997年1月至1998年8月31日）

The Zucker diabetic fatty rat is a well accepted model of human obesity and NIDDM. Animals inheriting a defect in the leptin receptor (fa/fa) develop early obesity insulin resistance and in males, NIDDM due to their leptin resistance. We have demonstrated that spectral analysis of whole body fat content detects the pre-obese (fa/fa) genotype before gross obesity and other metabolic derangements develop. In addition, this analysis provides a measure of lean body mass using our previous validated technique of fat and whole body water detection. We are finding that this animal model has a co-existent defect in lean body mass accumulation. Paradoxically in a second model using i.c.v. leptin infusion into normal rats, we are observing accelerated lean body mass loss in addition to augmented fat oxidation mediated by the central effects of leptin. Hyperinsulinemic glucose clamp studies in these two animal models suggest that there is strong correlation between intramyocellular triglyceride content and insulin sensitivity. We have been able to specifically monitor intramyocellular lipids through the use of proton spectroscopy and have previously validated its use in dogs and rabbits using the 1.5T clinical MR system at the Rogers MR Center. Studies are currently in progress to better understand the relationship between amounts and types of dietary fats, leptin, leptin resistance, intra-myocellular triglyceride stores and the development of insulin resistance and impaired insulin secretory response. (Service 5) REPORT PERIOD: (09/01/97-08/31/98)