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: 7483730
• 负责人: MAHMOOD S MOZAFFARI
• 金额: $ 18.01万
• 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 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7483730
• 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）：提出铬酸铬（CR（PIC）3）作为辅助治疗葡萄糖耐受性受损/ 2型糖尿病，因为它可以改善葡萄糖代谢。改善的血糖控制应保持肾功能，因为氧化应激（慢性高血糖的主要续集）对糖尿病性肾病的发病机理重要贡献。另一方面，肾脏不仅是铬消除的主要途径，而且是优先积聚它的器官。因此，在与肾功能改变有关的条件下，Cr（PIC）3对肾脏的影响需要仔细研究。我们表明，慢性治疗单态切除术，但具有CR（PIC）3的正常血糖大鼠提高了它们处置盐量挑战的能力。由于单次切除型大鼠随着年龄的增长而发展出肾功能受损，因此CR（PIC）3对高血糖状态的肾脏的有益作用将变得更加突出，因为血糖控制的伴随改善了。具体目的1，检验了以下假设：慢性CR（PIC）3治疗与氧化应激的生物标志物的减少相关，例如氧化应激的生物标志物，例如氧化谷胱甘肽，丙二酰二甲醛，晚期糖化终极产物和DNA损伤。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。特定目标3列出了以下假设：慢性CR（PIC）3治疗以及葡萄糖代谢的相关改善可以改善糖尿病肾脏的结构改变。研究将利用遗传（例如肥胖的Zucker大鼠和DB/DB小鼠）和非遗传（高血压 - 葡萄糖不耐受的大鼠）动物模型的疾病模型，这些模型显示出肾功能和结构中的危险。此外，我们将确定疾病状态是否影响铬的肾脏组织含量。总体而言，结果应洞悉CR（PIC）3在其使用情况下的肾脏影响中，这一方面受到了很少的关注。此外，这些研究将解决有关CR（PIC）3的层生成潜力的普遍关注和争议，这是使用2型糖尿病的相关动物模型尚待建立的方面。

项目成果

Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage.

• DOI: 10.1016/j.jnutbio.2011.05.004
• 发表时间: 2012-08
• 期刊: The Journal of nutritional biochemistry
• 作者: Mozaffari MS;Baban B;Abdelsayed R;Liu JY;Wimborne H;Rodriguez N;Abebe W
• 通讯作者: Abebe W

Chromium-picolinate therapy in diabetes care: individual outcomes require new guidelines and navigation by predictive diagnostics.

吡啶甲酸铬治疗糖尿病护理：个体结果需要新的指南和预测诊断的指导。

• DOI: 10.2174/187152612804142215
• 发表时间: 2012
• 期刊: Infectious disorders drug targets
• 作者: Yeghiazaryan,Kristina;Schild,HansH;Golubnitschaja,Olga
• 通讯作者: Golubnitschaja,Olga

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms and new guidelines.

吡啶甲酸铬治疗糖尿病护理：分子和亚细胞分析揭示了个体结果预测、个性化治疗算法和新指南的必要性。

• DOI: 10.2174/187152611795589717
• 发表时间: 2011
• 期刊: Infectious disorders drug targets
• 作者: Yeghiazaryan,Kristina;Peeva,Viktoriya;Shenoy,Aparna;Schild,HansH;Golubnitschaja,Olga
• 通讯作者: Golubnitschaja,Olga