Targeting cellular bioenergetics for the prevention and treatment of diabetes

针对细胞生物能量学预防和治疗糖尿病

• 批准号: 8150760
• 负责人: Francisco J Villarreal
• 金额: $ 45.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8150760
• 关键词: Adverse effects; Affect; Bioenergetics; Biogenesis; Cacao Plant; Cardiovascular system; Cause of Death; Data; Diabetes Mellitus; Direct Costs; Disease; Dose; Facilities and Administrative Costs; Flavanol; Flavonoids; Functional disorder; Instruction; Insulin; Insulin Resistance; Interdisciplinary Study; Mitochondria; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Pathology; Pharmaceutical Preparations; Prediabetes syndrome; Prevalence; Prevention; Receptor Cell; Reporting; Safety; Scientist; Seeds; Therapeutic; Therapeutic Agents; cellular targeting; diabetic; epicatechin; experience; mitochondrial dysfunction; novel; response

DESCRIPTION (provided by applicant): Diabetes is the fastest growing disease in the USA (mirroring increases in obesity rates) and is rising as a leading cause of death mostly from cardiovascular related pathologies. The current prevalence of diabetes is ~9% with a further ~30% as pre-diabetics. Estimated 2007 direct and indirect costs of diabetes in the USA are $174 billion. Compelling evidence has emerged implicating mitochondrial dysfunction in the pathophysiology of obesity, insulin resistance and type 2 diabetes. Insulin sensitizing agents used for the treatment of diabetes such as thiazoledinediones (TZDs) induce mitochondrial biogenesis and this may partly explain their therapeutic action. In spite of their therapeutic benefit they however, have the potential for serious side-effects. Flavonoids as TZDs have been reported to induce mitochondrial biogenesis favorably impacting cellular and organ bioenergetics. This class of natural compounds is in general, recognized as safe. However, their possible use as drugs for the treatment of pre-diabetes or diabetes has been poorly explored. Under this proposal, entitled "Targeting cellular bioenergetics for the treatment of pre-diabetes and diabetes: A team approach", we will create a highly integrated, multidisciplinary research team specifically assembled to systematically explore the prospect of the cacao flavanol (-)-epicatechin (and novel synthetic derivatives) to favorably affect cellular/organ bioenergetics. We intend to gather preliminary data to dispel the common notion that flavanols act mainly as antioxidans and that "the higher the dose, the greater the effect". Rather, we intend to generate evidence pertaining to their effect on specific cell receptors acting within specific dose-response profiles. During this initial seed period, we will fully assemble and integrate a unique and highly-experienced team consisting of basic scientists (molecular and organ physiologists) and translational experts to systematically examine the promise of epicatechin and novel derivatives as agents for the treatment of pre-diabetes and diabetes.

描述（由申请人提供）：糖尿病是美国增长最快的疾病（肥胖率的增加），并且正在成为主要死亡的主要原因，主要是与心血管相关的病理。糖尿病的当前患病率〜9％，糖尿病的进一步为糖尿病患者。估计美国糖尿病的2007年直接和间接成本为1740亿美元。令人信服的证据已经出现，暗示了线粒体功能障碍在肥胖，胰岛素抵抗和2型糖尿病的病理生理学中。胰岛素敏化剂用于治疗诸如噻唑烷二酮（TZD）（TZDS）等糖尿病诱导线粒体生物发生，这可能部分解释其治疗作用。尽管具有治疗益处，但它们仍具有严重的副作用。据报道，类黄酮作为TZD诱导线粒体生物发生有利地影响细胞和器官生物能学。这类天然化合物通常是安全的。但是，它们可能用作治疗糖尿病或糖尿病治疗的药物的使用很差。在此提案下，标题为“针对糖尿病前和糖尿病治疗的细胞生物能力：一种团队方法”，我们将创建一个高度成熟的，多学科的研究团队，专门组装，以系统地探索可可Flavanol（ - ） - epicatechin（和新颖的综合派生）的前景。我们打算收集初步数据，以消除亚麻酚主要充当抗毒剂的共同观念，并且“剂量越高，效果越大”。相反，我们打算产生与它们对特定剂量反应概况中作用的特定细胞受体的影响有关的证据。在这个最初的种子时期，我们将完全组装并整合由基本科学家（分子和器官生理学家）组成的独特且经验丰富的团队，并进行转化专家，以系统地研究Epicatechin和新颖的衍生品作为治疗前糖尿病和糖尿病的衍生物的希望。