Novel action of grape skin components on postprandial hyperglycemia

葡萄皮成分对餐后高血糖的新作用

基本信息

批准号：
8720700
负责人：
Kequan zhou
金额：
$ 41.69万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8720700
关键词：
Abdomen Acarbose Acute Adverse effects Affect American Amylases Animals Anthocyanins Antidiabetic Drugs Antioxidants Biological Blood Glucose Carbohydrates Catechin Clinical Research Clinical Trials Data Development Diabetes Mellitus Diabetes prevention Diabetic mouse Diarrhea Diet Dietary Intervention Dietary Supplementation Dietary intake Digestion Drug Targeting Eating Enzymes Fermentation Future Glucose Glucosidase Inhibitor Goals Grapes Hepatic Human Hyperglycemia In Vitro Individual Inflammatory Intake Intervention Studies Intestines Large Intestine Lead Mediating Modeling Mus Non-Insulin-Dependent Diabetes Mellitus Nutritional Obese Mice Oral Pharmaceutical Preparations Pre-Clinical Model Prediabetes syndrome Preparation Prevention Public Health Reaction Resveratrol Role Safety Skin Specificity Staging Starch Stress Supplementation Testing Toxic effect Translations United States Weight Gain absorption base conventional therapy cost db/db mouse diabetes control diabetes management diabetic dietary antioxidant dietary starch endothelial dysfunction evidence base gastrointestinal glucose output glucose uptake glucosidase glycemic control impaired glucose tolerance improved inhibitor/antagonist insight insulin secretion mouse model novel pandemic disease pre-clinical prevent public health relevance

Abdomen Acarbose Acute Adverse effects Affect American Amylases Animals Anthocyanins Antidiabetic Drugs Antioxidants Biological Blood Glucose Carbohydrates Catechin Clinical Research Clinical Trials Data Development Diabetes Mellitus Diabetes prevention Diabetic mouse Diarrhea Diet Dietary Intervention Dietary Supplementation Dietary intake Digestion Drug Targeting Eating Enzymes Fermentation Future Glucose Glucosidase Inhibitor Goals Grapes Hepatic Human Hyperglycemia In Vitro Individual Inflammatory Intake Intervention Studies Intestines Large Intestine Lead Mediating Modeling Mus Non-Insulin-Dependent Diabetes Mellitus Nutritional Obese Mice Oral Pharmaceutical Preparations Pre-Clinical Model Prediabetes syndrome Preparation Prevention Public Health Reaction Resveratrol Role Safety Skin Specificity Staging Starch Stress Supplementation Testing Toxic effect Translations United States Weight Gain absorption base conventional therapy cost db/db mouse diabetes control diabetes management diabetic dietary antioxidant dietary starch endothelial dysfunction evidence base gastrointestinal glucose output glucose uptake glucosidase glycemic control impaired glucose tolerance improved inhibitor/antagonist insight insulin secretion mouse model novel pandemic disease pre-clinical prevent public health relevance

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项目摘要

DESCRIPTION (provided by applicant): Diabetes has become a major public health problem and is emerging as a pandemic. There is a strong need for developing novel complementary and alternative strategies for controlling diabetes. Our long-term goal is to develop a safe and effective nutritional intervention to support diabetes prevention and treatment. The objective of this application is to identify novel unique ¿-glucosidase-inhibiting components in GSE, to elucidate the role of these components in lowering postprandial hyperglycemia, and to further assess the safety and efficacy of the GSE components in preclinical models for preventing and treating type-2 diabetes. GSE is a nutritional antioxidant supplement used frequently by the American public. We have recently found that that GSE intake exerts a novel inhibitory activity on postprandial hyperglycemia in diabetic mice, which is related to its specific inhibition of intestinal ¿-glucosidases. Furthermore, we showed that dietary supplementation of GSE significantly reduced blood glucose in diet-induced obese mice independent of its effects on food intake, weight gain, or antioxidant activity. More recently, we demonstrated that oral intake of GSE significantly reduced postprandial blood glucose in humans. We therefore hypothesize that the novel inhibitory action of GSE on postprandial hyperglycemia is primarily mediated by specific inhibition of intestinal ¿-glucosidases, and GSE and its active components could be developed and used as a safe and targeted nutritional intervention to support diabetes prevention and treatment. To test our hypothesis, we will pursue three aims: Aim 1 is to identify active ¿-glucosidase-inhibiting components in GSE and further determine their inhibitory mechanisms. We will employ an activity-driven approach to isolate and identify active components in GSE. We will then determine their specificity, inhibitory mode, and possible additive/synergistic effects on specific ¿- glucosidases. Aim 2 is to determine mechanisms underlying the novel inhibitory action of GSE on postprandial hyperglycemia. We will use a type-2 diabetic model to determine whether active ¿-glucosidase-inhibiting components are responsible for lowering postprandial hyperglycemia; and whether these components primarily act on ¿-glucosidases to ameliorate postprandial hyperglycemia. Aim 3 is to determine the efficacy and safety of GSE components in preclinical models for preventing and treating type-2 diabetes. We will perform three studies: Study 1 is an acute intake study to determine the most effective GSE preparation for treating postprandial hyperglycemia in db/db mice; Study 2 is to determine whether dietary supplementation of our GSE preparation can prevent the onset of diet-induced diabetes in diet-induced obese mice; and Study 3 is to determine whether our GSE preparation, following the onset of diabetes, can improve glycemic control in db/db mice. This transitional study will provide important preclinical data regarding the antidiabetic mechanisms, biological efficacy, and safety of GSE that should facilitate eventual translation into future clinical studies to assess GSE and its components as a safe, low cost, and evidence-based nutritional intervention for diabetes.

描述（由应用程序提供）：糖尿病已成为一个主要的公共卫生问题，并且正成为大流行。强烈需要开发新颖的完整性和控制糖尿病的替代策略。我们的长期目标是开发安全有效的营养干预措施，以支持预防糖尿病和治疗。该应用的目的是识别GSE中新型独特的 - 葡萄糖苷酶抑制成分，以阐明这些成分在降低餐后高血糖症中的作用，并进一步评估GSE成分在预防和治疗2型糖尿病中的抗螺旋线模型中GSE成分的安全性和效率。 GSE是美国公众经常使用的营养抗氧化剂补充剂。我们最近发现，GSE摄入对糖尿病小鼠的餐后高血糖症具有新颖的抑制活性，这与其对肠道» - 葡萄糖苷酶的特异性抑制有关。此外，我们表明，对饮食诱导的肥胖小鼠的饮食补充显着降低了血糖对食物摄入，体重增加或抗氧化活性的影响。最近，我们证明了口服GSE的口服摄入可显着降低人类的餐后血糖。因此，我们假设GSE对餐后高血糖的新型抑制作用是由特异性抑制肠» - 葡萄糖苷酶的特异性介导的，并且GSE及其活性成分可以开发，并可以用作安全且靶向的营养干预措施，以支持预防糖尿病和治疗。为了检验我们的假设，我们将追求三个目标：目标1是识别GSE中的主动» - 葡萄糖苷酶抑制成分，并进一步确定其抑制机制。我们将采用一种活动驱动的方法来隔离和识别GSE中的主动组件。然后，我们将确定它们的特异性，抑制模式以及可能对特定葡萄糖酶的添加剂/协同作用。目的2是确定GSE对餐后高血糖的新型抑制作用的基础机制。我们将使用2型糖尿病模型来确定活性�-葡萄糖苷酶抑制成分是否负责降低餐后高血糖；这些成分是否对�-葡萄糖苷酶的作用是否可以改善餐后高血糖。 AIM 3是确定GSE组件在临床前模型中预防和治疗2型糖尿病的有效性和安全性。我们将进行三项研究：研究1是一项急性摄入研究，旨在确定用于治疗餐后高血糖db/db小鼠的最有效的GSE准备。研究2是为了确定饮食补充我们的GSE制剂是否可以防止饮食诱发的糖尿病发作。在饮食引起的肥胖小鼠中；研究3是为了确定我们的GSE制剂是否在糖尿病开始后是否可以改善DB/DB小鼠的血糖控制。这项过渡性研究将提供有关GSE抗糖尿病机制，生物学效率和安全性的重要临床前数据，这些数据应促进最终转化为未来的临床研究，以评估GSE及其成分作为安全，低成本和基于证据的糖尿病营养干预措施。