Novel action of grape skin components on postprandial hyperglycemia

葡萄皮成分对餐后高血糖的新作用

• 批准号: 8578514
• 负责人: Kequan zhou
• 金额: $ 38.28万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 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/8578514
• 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; Functional disorder; 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; 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

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（由申请人提供）：糖尿病已成为一个主要的公共卫生问题，并且正在成为一种流行病，迫切需要开发新的补充和替代策略来控制糖尿病。支持糖尿病预防和治疗的营养干预该应用的目的是识别新颖独特的¿ -GSE 中的葡萄糖苷酶抑制成分，阐明这些成分在降低餐后高血糖方面的作用，并进一步评估 GSE 成分在预防和治疗 2 型糖尿病的临床前模型中的安全性和有效性 GSE 是一种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有一种新的抑制活性，这与其有关。肠道特异性抑制 ¿此外，我们发现，膳食补充 GSE 可以显着降低饮食诱导的肥胖小鼠的血糖，而与其对食物摄入、体重增加或抗氧化活性的影响无关。最近，我们证明口服 GSE 可以显着降低餐后血糖。因此，我们发现 GSE 对餐后高血糖的新抑制作用主要是通过对肠道的特异性抑制来介导的。 -葡萄糖苷酶、GSE 及其活性成分可以开发并用作安全且有针对性的营养干预措施，以支持糖尿病的预防和治疗。为了检验我们的假设，我们将追求三个目标：目标 1 是确定活性成分。 -GSE 中的葡萄糖苷酶抑制成分，并进一步确定其抑制机制，我们将采用活性驱动的方法来分离和鉴定 GSE 中的活性成分，然后我们将确定它们的特异性、抑制模式以及对特定 ¿ - 葡萄糖苷酶。目标 2 是确定 GSE 对餐后高血糖的新型抑制作用的机制。我们将使用 2 型糖尿病模型来确定是否活跃。 -葡萄糖苷酶抑制成分负责降低餐后高血糖；以及这些成分是否主要作用于 ¿ -葡萄糖苷酶改善餐后高血糖。目标 3 是确定 GSE 成分在预防和治疗 2 型糖尿病的临床前模型中的有效性和安全性：研究 1 是一项急性摄入研究，旨在确定最有效的 GSE。用于治疗 db/db 小鼠餐后高血糖的制剂；研究 2 是确定膳食补充我们的 GSE 制剂是否可以预防饮食诱发的血糖升高研究 3 是为了确定我们的 GSE 制剂在糖尿病发作后是否可以改善 db/db 小鼠的血糖控制，这项过渡性研究将提供有关抗糖尿病机制、生物学功效的重要临床前数据。以及 GSE 的安全性，这应该有助于最终转化为未来的临床研究，以评估 GSE 及其组成部分作为糖尿病的安全、低成本和循证营养干预措施。