Is chromium picolinate renoprotective in diabetes?

描述（由申请人提供）：吡啶甲酸铬（Cr(pic)3）被建议作为糖耐量受损/ 2型糖尿病的辅助治疗，因为它可以改善葡萄糖代谢。改善血糖控制可以保护肾功能，因为氧化应激是慢性高血糖的主要后遗症，在糖尿病肾病的发病机制中起重要作用。另一方面，肾脏不仅是消除铬的主要途径，而且是优先积累铬的器官。因此，在与肾功能改变相关的情况下，Cr(pic)3对肾脏的影响需要仔细研究。我们发现，对未切除肾但血糖正常的大鼠进行Cr(pic)3慢性治疗可提高其处理生理盐水容量挑战的能力。由于未切除肾的大鼠随着年龄的增长肾功能受损，因此Cr(pic)3对高血糖状态肾脏的有益作用可能更加突出，因为它会改善血糖控制。特异性目标1，验证慢性Cr(pic)3治疗改善血糖控制与氧化应激生物标志物（如氧化谷胱甘肽、丙二醛、晚期糖基化终产物和DNA损伤）减少相关的假设。特异性目的2验证了Cr(pic)3对葡萄糖代谢的有益作用会改善肾功能的假设。特异性目的3验证了慢性Cr(pic)3治疗以及相关的糖代谢改善可以改善糖尿病肾脏结构改变的假设。研究将利用遗传性（如肥胖Zucker大鼠和db/db小鼠）和非遗传性（高血压-葡萄糖不耐受大鼠）动物模型，这些动物模型显示出肾脏功能和结构的紊乱。此外，我们将确定疾病状态是否影响肾组织中铬的含量。总的来说，这些结果应该为Cr(pic)3在提倡使用的健康和疾病条件下的肾脏作用提供见解，这方面受到的关注太少。此外，这些研究将解决目前关于Cr(pic)3的致裂潜能的关注和争议，这方面仍有待通过相关的2型糖尿病动物模型来建立。

DESCRIPTION (provided by applicant): Chromium picolinate (Cr(pic)3) is proposed as adjuvant therapy for impaired glucose tolerance/ type 2 diabetes mellitus because it improves glucose metabolism. Improved glycemic control should preserve renal function because oxidative stress, a major sequel of chronic hyperglycemia, contributes importantly to pathogenesis of diabetic nephropathy. On the other hand, the kidney is not only the principal route of elimination for chromium but also an organ that preferentially accumulates it. Thus the impact of Cr(pic)3 on the kidney in conditions associated with altered renal function requires careful study. We show that chronic treatment of uninephrectomized, but normoglycemic rats with Cr(pic)3 improves their ability to dispose of a saline volume challenge. Since the uninephrectomized rats develop impaired renal function with age, it is plausible that the beneficial effects of Cr(pic)3 on the kidney in hyperglycemic states would be even more prominent because of attendant improvement in glycemic control. Specific Aim 1, tests the hypothesis that chronic Cr(pic)3 therapy improves glycemic control in association with reduction in biomarkers of oxidative stress such as oxidized glutathione, malonyldialdehyde, advanced glycation end products and DNA damage. Specific Aim 2 tests the hypothesis that the beneficial effect of Cr(pic)3 on glucose metabolism will improve renal function. Specific Aim 3 testes the hypothesis that chronic Cr(pic)3 treatment, and associated improvement in glucose metabolism, ameliorates structural alterations of the diabetic kidney. The studies will utilize genetic (e.g, obese Zucker rat and db/db mouse) and non-genetic (hypertensive-glucose intolerant rat) animal models of the disease which display derangements in renal function and structure. In addition, we will determine whether the disease state affects renal tissue content of chromium. Collectively, the results should provide insight into renal effects of Cr(pic)3 in health and disease conditions for which its use is advocated, an aspect that has received too little attention. Further, the studies will address the prevailing concern and controversy regarding clastogenic potential of Cr(pic)3, an aspect that remains to be established using relevant animal models of type 2 diabetes.