Chromium treatment of Obesity-related insulin resistance

铬治疗肥胖相关的胰岛素抵抗

基本信息

批准号：
7230012
负责人：
DENNIS C MYNARCIK
金额：
$ 22.58万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-15 至 2009-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7230012
关键词：
1-Phosphatidylinositol 3-Kinase 2,4-thiazolidinedione 8-hydroxy-2&apos -deoxyguanosine A549 Abdominal Pain Acarbose Acids Acute Kidney Failure Address Adipocytes Adipose tissue Adult Adverse effects Adverse event Aftercare American Appendix Attention Benzene Biguanides Binding Blood Body Weight Body Weight decreased Body mass index Bos taurus Breathing Calcium Calcium-Binding Proteins Calmodulin Carbon Dioxide Carcinogens Cardiovascular Diseases Case Study Cattle Cell Nucleus Cell membrane Cells Centers for Disease Control and Prevention (U.S.)China Chinese Hamster Ovary Cell Chinese People Chinese Traditional Medicine Cholesterol Chromium Chromium Picolinate Chromosome abnormality Classification Clinical Clinical Research Complementary and alternative medicine Complex Condition Controlled Study Coronary Arteriosclerosis Culture Media DNA DNA Damage Daily Data Development Diabetes Mellitus Diabetes prevention Diagnostic Diarrhea Dietary Supplementation Dietary intake Disease Dose Drosophila genus Drosophila melanogaster Early treatment Economics Enzymes Euglycemic Clamping Evaluation Excretory function Failure Fasting Fatty acid glycerol esters Foxes Functional disorder Generations Glucose Glucose Clamp Glucose Intolerance Glucose Plasma Concentration Glucose Transporter Glycogen Synthase Kinase 3 Glycogen Synthase Kinases Glycosylated Hemoglobin Glycosylated hemoglobin A Grant HIV Hamsters Health Health Care Costs Hemoglobin Hepatic Hormones Hour Human In Vitro Incidence Individual Ingestion Insulin Insulin Receptor Insulin Resistance Insulin Signaling Pathway Intake Intervention Intravenous Ions Irritants Kidney Kidney Failure Kinetics Lactic Acidosis Larva Lead Life Life Style Link Lipolysis Liver Lung Maintenance Measurement Measures Mediating Membrane Metformin Minerals Modality Modeling Molecular Conformation Molecular Weight Monitor Morbidity - disease rate Muscle Mutagenesis Mutation NIH Program Announcements National Health and Nutrition Examination Survey Nicotinic Acids Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Numbers OGTT Obesity Oligopeptides Oral Other Genetics Ovarian Overdose Overweight Oxidative Stress Pancreas Pathway interactions Patients Peptides Peripheral Pharmaceutical Preparations Phenformin Phosphorylation Phosphotransferases Pioglitazone Placebos Plasma Polycystic Ovary Syndrome Population Prevalence Prevention Prevention intervention Protein Tyrosine Kinase Proteins Proto-Oncogene Proteins c-akt Public Health Purpose Rate Rattus Regulation Renal function Reporting Research Research Personnel Resistance Resistance development Risk Risk Factors Role SLC2A1 gene Safety Serum Signal Transduction Source Staging Statistically Significant Suggestion Sulfonylurea Compounds Supplementation Syndrome Techniques Testing Therapeutic Thiazolidinediones Thinking Time Tissues Total Parenteral Nutrition Toxic effect Tyrosine Phosphorylation Urine Work Yeasts absorption base carbohydrate metabolism chromium deficiency clinically significant cost cost effective day design diabetes prevention program diabetic dietary supplements gastrointestinal glucose disposal glucose tolerance glucose transport glucose uptake glucosidase health care economics impaired glucose tolerance improved in vivo insulin receptor substrate 1 protein insulin receptor tyrosine kinase insulin secretion insulin sensitivity insulin signaling insulin tolerance intravenous glucose tolerance test mortality nicotinate obesity treatment pandemic disease picolinate placebo controlled study prevent programs receptor repaglinide respiratory response rosiglitazone troglitazone urinary

项目摘要

DESCRIPTION (provided by applicant): The rising incidence of obesity is implicated in increased health risks including cardiovascular disease and diabetes. However, the Diabetes Prevention Program has demonstrated that early treatment of insulin resistance can reduce progression to overt diabetes. Since insulin resistance is also an independent risk factor for cardiovascular disease, early treatment would provide additional benefit. Chromium picolinate is a dietary supplement that has been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus. Since prevention of diabetes may be preferable to treatment, this proposal will concentrate on the effect of chromium supplementation in obese (BMI greater than 30) subjects with insulin resistance, but without overt diabetes. We have preliminary data demonstrating that chromium supplements improve insulin sensitivity in patients with both HIV disease and polycystic ovarian syndrome. Specific Aim 1 of this proposal will examine the safety and efficacy of supplemental chromium picolinate in the treatment of insulin resistance in obesity-related insulin resistance. Quantitative improvements in insulin-mediated glucose disposal will be determined in a placebo-controlled study of chromium supplementation with 1000ug (19.2 umol) of chromium as chromium picolinate, over a 2-month course of therapy of subjects with glucose intolerance (defined with an oral glucose tolerance test, OGTT). Both safety (liver and renal function and oxidative stress) and efficacy (improved glucose disposal with a hyperinsulineminc, euglycemic clamp and insulin secretion, OGTT) will be evaluated. In vitro studies have demonstrated that chromium (as chromodulin) enhances the activity of the insulin receptor. Specific Aim 2 will assess the mechanism by which chromium supplementation improves insulin action. Specifically, this aim will access changes in plasma free fatty acids, the ability of insulin to suppress lipolysis in adipose tissue, and insulin signaling in adipose tissue including the phosphorylation of insulin receptor substrate 1 and activity of downstream enzymes such as glycogen synthase kinase 3B. Thus, this research will document the therapeutic benefit of chromium supplementation for insulin resistance/glucose intolerance and will also provide a mechanistic framework to explain how chromium supplementation enhances insulin action.

描述（由申请人提供）：肥胖发病率的上升与心血管疾病和糖尿病等健康风险的增加有关。然而，糖尿病预防计划已经证明，早期治疗胰岛素抵抗可以减少进展为明显的糖尿病。由于胰岛素抵抗也是心血管疾病的独立危险因素，因此早期治疗将提供额外的益处。吡啶甲酸铬是一种膳食补充剂，已被证明可以改善 2 型糖尿病患者的胰岛素敏感性。由于预防糖尿病可能比治疗更可取，因此该提案将重点关注补充铬对患有胰岛素抵抗但无明显糖尿病的肥胖（BMI 大于 30）受试者的影响。我们的初步数据表明，铬补充剂可以改善艾滋病毒和多囊卵巢综合征患者的胰岛素敏感性。该提案的具体目标 1 将检查补充吡啶甲酸铬在治疗肥胖相关胰岛素抵抗中的安全性和有效性。胰岛素介导的葡萄糖处理的定量改善将在一项安慰剂对照研究中确定，该研究对患有葡萄糖不耐受的受试者（定义为口服葡萄糖酸）进行为期 2 个月的治疗，以 1000 微克（19.2 微摩尔）的铬形式补充铬（吡啶甲酸铬）。葡萄糖耐量试验（OGTT）。将评估安全性（肝肾功能和氧化应激）和功效（通过高胰岛素、正常血糖钳夹和胰岛素分泌，OGTT 改善葡萄糖处理）。体外研究表明，铬（作为染色调节蛋白）可增强胰岛素受体的活性。具体目标 2 将评估补充铬改善胰岛素作用的机制。具体来说，该目标将了解血浆游离脂肪酸的变化、胰岛素抑制脂肪组织脂解的能力以及脂肪组织中的胰岛素信号传导，包括胰岛素受体底物 1 的磷酸化和下游酶（如糖原合酶激酶 3B）的活性。因此，这项研究将记录补充铬对胰岛素抵抗/葡萄糖不耐受的治疗益处，并将提供一个机制框架来解释补充铬如何增强胰岛素作用。