Bioactives in Blueberries and Insulin Resistance

蓝莓中的生物活性物质和胰岛素抵抗

基本信息

批准号：
8384431
负责人：
April Stull
金额：
$ 12.47万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8384431
关键词：
1-Phosphatidylinositol 3-Kinase 5&apos -AMP-activated protein kinase Address Adipocytes Adipose tissue Adverse event Animals Anthocyanins Antioxidants Area Biological Biological Factors Blueberries Botanicals Canada Cell Culture Techniques Ceramides Clinical Clinical Data Clinical Trials Complementary and alternative medicine Consumption Data Development Dietary Supplementation Disease Effectiveness Euglycemic Clamping Fatty acid glycerol esters Folk Remedy Fractionation Fruit Funding Glucose Clamp Goals Health Health Benefit Hepatic Human In Vitro Individual Insulin Insulin Receptor Insulin Resistance Intervention Intracellular Signaling Proteins Knowledge Laboratories Learning Liver Measures Mentors Metabolic Methodology Modeling Molecular and Cellular Biology Mus Muscle Fibers Myoblasts Non-Insulin-Dependent Diabetes Mellitus Obesity Oral Administration Palmitates Pathway interactions Personal Satisfaction Pharmacological Treatment Phosphorylation Phytochemical Placebos Population Prediabetes syndrome Property Proteins Public Health Publishing Quality of life Reporting Research Research Personnel Rodent Site Skeletal Muscle Supplementation Techniques Testing Therapeutic Therapeutic Intervention Tissues Training Treatment Efficacy Work base blood glucose regulation career career development dietary supplements feeding glucose disposal glucose production glucose uptake improved in vivo insight insulin sensitivity insulin signaling novel pre-clinical research study response

项目摘要

DESCRIPTION (provided by applicant): Insulin resistance is a key pathophysiologic feature of pre-diabetes and a major contributor to the progression towards overt type 2 diabetes mellitus (T2DM). For many years, increased consumption of bioactives in blueberries (BB) has been a folk remedy in Canada for treating T2DM. Preliminary data in the applicant's laboratory found that dietary supplementation with BB for six weeks was well tolerated and increased whole-body insulin sensitivity in humans with pre-diabetes when compared to the placebo group. However, cellular mechanisms of action underlying the biological response of BB in improving insulin sensitivity were not evaluated previously. Therefore, the overall research objective in the application is to determine the underlying cellular mechanism(s) of action and therapeutic efficacy of BB and its bioactive component(s) in modulating insulin sensitivity in target tissues i vitro and in vivo. To attain the overall objective, the working hypothesis will be tested that BB wll improve insulin sensitivity by modulating glucose uptake and intracellular proteins in the insulin-dependent (i.e., Insulin receptor (IR), insulin receptor substrate (IRS), phosphatidylinositol-3 kinase (PI-3K), and Akt)) and -independent (i.e., AMP-activated protein kinase (AMPK)) pathways in target tissues in vitro and in vivo. The hypothesis will be addressed through the following Specific Aims: 1) determine cellular mechanism(s) by which whole BB enhances insulin sensitivity in insulin sensitive tissues in vitro (i.e., adipose and skeletal muscle cell cultures), 2) isolate and identify the bioactive component(s) in BB and their mechanism(s) of action by which insulin sensitivity is enhanced in insulin sensitive tissues in vitro, and 3) evaluate the therapeutic efficacy and tissue-specific site of action (i.e., liver, adipose tissue, and/or skeletal muscle) of whole BB and BB bioactive component(s) on ameliorating insulin sensitivity in mice using the hyperinsulinemic-euglycemic clamp. During this mentored career development, Dr. Stull will acquire detailed input from her mentors with relevant expertise and work to increase her versatility as a clinical researcher by learning new techniques and methodologies related to [molecular and cellular biology, botanical characterization, and animal biomethodology. Dr. Stull's long-term goal is to become an independent translational CAM investigator and leader in the study of complementary and alternative medicine with an emphasis in botanical dietary supplementation and its impact on insulin resistance. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because it will provide new insights on the effectiveness of phytochemicals found in a common fruit (i.e., blueberries) on glucose control and insulin sensitivity, which would potentially benefit the health quality of life, and well-being of an insulin-resistant population. Most importantly, the findings from this application will enable consumers to make more informed decisions about the use of bioactives in blueberries to treat insulin resistance in individuals with pre-diabetes or type 2 diabetes.

描述（由申请人提供）：胰岛素抵抗是糖尿病前的关键病理生理特征，也是向公开2型糖尿病（T2DM）发展的主要贡献者。多年来，蓝莓（BB）中生物活性剂的消费量增加一直是加拿大治疗T2DM的一种民间疗法。申请人实验室中的初步数据发现，与安慰剂组相比，在患有糖尿病前的人类中，用BB饮食补充六周，并且全身胰岛素敏感性提高。然而，先前未评估BB在改善胰岛素敏感性中生物学反应的作用的细胞机制。因此，应用程序的总体研究目标是确定BB及其生物活性成分在调节靶组织I体外和体内调节胰岛素敏感性方面的作用和治疗功效的潜在细胞机制。为了达到总体目标，将测试工作假设，即通过调节胰岛素依赖性（即胰岛素受体（IR），胰岛素受体（IRS），胰岛素受体（IRS），磷脂酰蛋白固醇-3kinase（phosphationyositol-3kinase）（phosphationysitol-3kinase（p-i-3k），以及依赖性a和aindestrestement）（即胰岛素受体（IR），以及I. pi-i-3k），以及依赖于胰岛素受体（IRS），以及依赖于胰岛素受体（IR），以及依赖于胰岛素受体（IR），以及I. AMP激活的蛋白激酶（AMPK）在体外和体内靶组织中的途径。该假设将通过以下特定目的解决：1）确定整个BB在体外增强胰岛素敏感组织中胰岛素敏感性（即脂肪和骨骼肌细胞培养）的胰岛素敏感性，2），2）隔离并确定BB的生物活性成分（S）在BB及其机制中的作用，从而使其在bb及其机制中的作用增强，从而使其在INSTINS IS insitive IS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS INSTINS IS固定在ISSING中。体外和3）评估整个BB和BB生物活性成分（肝脏，脂肪组织和/或骨骼肌肉）的治疗功效和组织特异性的作用部位（即使用高胰岛素 - e糖 - euguggempoomed clamp clamp clamp clamp clamp。在这一指导的职业发展期间，斯特尔博士将通过学习与[分子和细胞生物学，植物学特征和动物生物方法学有关的新技术和方法，从相关的专业知识中获得详细的意见，并努力提高她作为临床研究人员的多功能性。 Stull博士的长期目标是成为互补和替代医学研究的独立翻译CAM研究者和领导者，重点是补充植物饮食及其对胰岛素抵抗的影响。公共卫生相关性：拟议的研究与公共卫生有关，因为它将提供有关共同水果（即蓝莓）在葡萄糖控制和胰岛素敏感性中发现的植物化学物质的有效性的新见解，这可能会使健康的健康质量以及胰岛素耐药者的健康良好。最重要的是，该应用程序的发现将使消费者能够对蓝莓中生物活性剂的使用来治疗患有糖尿病前期或2型糖尿病患者的胰岛素抵抗的更明智的决定。