Is chromium picolinate renoprotective in diabetes?

吡啶甲酸铬对糖尿病有肾脏保护作用吗？

• 批准号: 7314246
• 负责人: MAHMOOD S MOZAFFARI
• 金额: $ 21.77万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7314246
• 关键词: Address; Adjuvant Therapy; Advanced Glycosylation End Products; Adverse effects; Advocate; Affect; Age; Albumins; Animal Disease Models; Animal Model; Animals; Attention; Binding; Biochemical; Biological Assay; Biological Markers; Biological Preservation; Cell Nucleus; Chromium; Chromium Picolinate; Chromosome Breakage; Chronic; Comet Assay; Complications of Diabetes Mellitus; Condition; Cytosol; DNA Damage; DNA Double Strand Break; Data; Diabetes Mellitus; Diabetic Nephropathy; Disease; Electrolytes; Excretory function; Functional disorder; Genetic; Glomerular Filtration Rate; Glucose; Glucose tolerance test; Glutathione; Glutathione Disulfide; Hand; Health; Homeostasis; Hyperglycemia; Hypertension; Immunoblotting; Impaired Renal Function; In Vitro; Injury; Insulin Receptor; Kidney; Kidney Diseases; Liquid substance; Malondialdehyde; Measurement; Metabolism; Mitochondria; Modeling; Molecular Weight; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Oxidative Stress; Pathogenesis; Patients; Pharmaceutical Preparations; Proteins; Rattus; Renal Plasma Flow; Renal Tissue; Renal function; Reporting; Risk; Route; Saline; Sodium; Structure; Supplementation; Testing; Testis; Therapeutic; Toxic effect; Treatment Efficacy; Zucker Rats; blood glucose regulation; clinically relevant; db/db mouse; diabetic; glucose metabolism; glucose tolerance factor; glycemic control; impaired glucose tolerance; improved; in vivo; insight; insulin signaling; interest; lipid metabolism; normotensive; oxidative DNA damage; research study; treatment effect; urinary

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.

描述（由申请人提供）：吡啶甲酸铬（Cr(pic)3）被提议作为糖耐量受损/2型糖尿病的辅助疗法，因为它改善葡萄糖代谢。改善血糖控制应该可以保护肾功能，因为氧化应激是慢性高血糖的主要后遗症，对糖尿病肾病的发病机制有重要影响。另一方面，肾脏不仅是铬的主要消除途径，也是优先积累铬的器官。因此，在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。我们表明，对未切除肾但血糖正常的大鼠进行 Cr(pic)3 长期治疗可提高其应对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会受损，因此在高血糖状态下 Cr(pic)3 对肾脏的有益作用可能会更加突出，因为血糖控制随之改善。具体目标 1 检验了这样的假设：长期 Cr(pic)3 疗法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）的减少相关。具体目标 2 检验了 Cr(pic)3 对葡萄糖代谢的有益作用将改善肾功能的假设。具体目标 3 检验了以下假设：长期 Cr(pic)3 治疗以及相关的葡萄糖代谢改善可改善糖尿病肾脏的结构改变。这些研究将利用该疾病的遗传（例如肥胖 Zucker 大鼠和 db/db 小鼠）和非遗传（高血压葡萄糖不耐受大鼠）动物模型，这些模型显示肾功能和结构紊乱。此外，我们还将确定疾病状态是否影响肾组织中铬的含量。总的来说，这些结果应该可以深入了解 Cr(pic)3 对健康和提倡使用 Cr(pic)3 的疾病状况的肾脏影响，而这一方面受到的关注太少。此外，这些研究将解决有关 Cr(pic)3 断裂潜力的普遍关注和争议，这一方面仍有待使用 2 型糖尿病的相关动物模型来确定。