Is chromium picolinate renoprotective in diabetes?

描述(申请人提供)：吡喃甲酸铬(Cr(Pic)3)被建议作为糖耐量受损/2型糖尿病的辅助治疗，因为它改善了葡萄糖代谢。改善的血糖控制应该保护肾功能，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着重要作用。另一方面，肾脏不仅是铬排出的主要途径，也是优先积累铬的器官。因此，在与肾功能改变相关的条件下，铬(Pic)3对肾脏的影响需要仔细研究。我们发现，对单肾切除但血糖正常的大鼠使用铬(Pic)3进行慢性治疗可以提高它们处理生理盐水容量挑战的能力。由于单肾切除大鼠的肾功能随着年龄的增长而受损，因此，在高血糖状态下，由于血糖控制的改善，铬(Pic)3对肾脏的有益作用可能会更加突出。具体目标1，测试假设，慢性铬(Pic)3治疗改善血糖控制与减少氧化应激的生物标记物，如氧化谷胱甘肽、丙二醛、晚期糖基化终产物和DNA损伤有关。特定目的2验证了这样一种假设，即铬(Pic)3对糖代谢的有益作用将改善肾功能。特定目标3验证了这样的假设，即慢性铬(Pic)3治疗以及相关的葡萄糖代谢的改善，改善了糖尿病肾脏的结构变化。这些研究将利用表现出肾脏功能和结构紊乱的遗传性(例如肥胖的Zucker大鼠和db/db小鼠)和非遗传性(高血压-葡萄糖耐受性大鼠)的疾病动物模型。此外，我们将确定疾病状态是否会影响肾组织中铬的含量。总而言之，这些结果应该能洞察铬(Pic)3在健康和疾病条件下对肾脏的影响，这是一个受到太少关注的方面。此外，这些研究将解决普遍存在的关于铬(Pic)3的碎裂潜能的关注和争议，这一方面仍有待使用相关的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.