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

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

展开

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）：肥胖的发生率上升与健康风险增加，包括心血管疾病和糖尿病。但是，预防糖尿病计划表明，胰岛素抵抗的早期治疗可以减少对明显的糖尿病的进展。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好处。 Picolinate Chromium picolinate是一种饮食补充剂，已显示可改善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，因此该建议将集中于肥胖（BMI大于30）受试者具有胰岛素抵抗的受试者的影响，但没有明显的糖尿病。我们有初步数据表明，铬补充剂可改善HIV疾病和多囊卵巢综合征患者的胰岛素敏感性。该提案的具体目的1将检查补充铬酸酯在肥胖相关胰岛素抵抗中胰岛素抵抗治疗胰岛素耐药性方面的安全性和功效。胰岛素介导的葡萄糖处置的定量改进将在安慰剂对照的研究中确定用1000ug（19.2 umol）作为铬酸铬铬酸铬铬铬酸铬的铬（19.2 umol），在用葡萄糖不耐受的受试者治疗2个月的治疗过程中（用口服粘液耐受性耐受性测试定义）。将评估安全性（肝脏和肾功能以及氧化应激）和功效（用高胰岛素蛋白，葡萄糖处置改善葡萄糖处置，euglycemic Clamp和胰岛素分泌，OGTT）。体外研究表明，铬（作为铬蛋白）增强了胰岛素受体的活性。具体目标2将评估铬补充改善胰岛素作用的机制。具体而言，此目标将获取无血浆脂肪酸的变化，胰岛素抑制脂肪组织中脂肪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的磷酸化以及诸如糖激素合酶基因酶3B等下游酶的磷酸化。因此，这项研究将记录补充铬抑制/葡萄糖不耐症的治疗益处，还将提供一个机械框架，以解释补充铬如何增强胰岛素作用。