Reduced Adipocytes FGF-21 Sensitivity as a Trigger for Type-2 Diabetes Development

约翰A。夏威夷大学（UH）的伯恩斯医学院（JABSOM）建议开发一种 位于夏威夷的多学科糖尿病卓越生物医学研究中心（COBRE）。 该中心最初将跨越部门，最终校园边界，以促进代谢健康的 夏威夷和太平洋地区的人民。该中心将利用夏威夷的能力， 糖尿病的潜在机制通过转化研究。总体目标是：1）指导初级 研究糖尿病和胰岛素抵抗（IR）的研究者，2）建立一个指导团队，3）开发一个 促进DM和IR研究的资源核心，4）使用试点开发未来的研究人员 项目计划，以及5）招聘一名具有翻译DM专业知识的副教授/正教授 research. 糖尿病的全球患病率持续增加，与此同时，肥胖症的存在不断扩大， 超重的成人和儿童。在美国，糖尿病的患病率现在影响到2790万儿童和成人 (8.9%的美国人口）（http：//www.diabetes.org/diabetes-basics/diabetics/）。在种族和族裔之间 在少数民族中，糖尿病患病率超过美国普通人群3倍。我们已经表明 在夏威夷原住民（NHs）中，DM的患病率为22.4%，另有15%被诊断为糖尿病。 葡萄糖耐量受损或糖尿病前期状态。事实上，先前关于DM、IR、代谢性疾病的流行病学研究 综合征（MetS）和心脏病危险因素在夏威夷的NHS和其他高风险种族人群中 提供了一个丰富的环境来开发这种新的COBRE，致力于了解分子 DM、IR和MetS的生物学基础。 COBRE资金将与机构资金一起利用，以加速卓越研究的发展 该中心的研究重点跨越了翻译谱，其中一项临床研究是在 夏威夷土著和太平洋岛民专注于糖尿病和免疫表观遗传学。动物和细胞 四项研究中有三项采用了模型，目的是研究骨骼肌中的阳离子通道、葡萄糖转运、 心肌细胞和脂肪细胞，以及糖尿病和慢性肾虚中的血管钙化和血脂异常 在IR和DM的背景下。本建议补充的新资源包括资助 表观遗传学，动物代谢表型和细胞代谢的资源核心。试点项目 还提议为2-3名新的调查员提供资金，因为初级调查员的初始队列正在向 研究独立性。JABSOM领导层还将招聘一名副教授/正教授，其研究 补充并重点关注翻译型DM和IR。

The John A. Burns School of Medicine (JABSOM) at the University of Hawaii (UH) proposes to develop a multidisciplinary Hawaii-based Center of Biomedical Research Excellence (COBRE) in Diabetes Mellitus (DM). This Center will initially span departmental and eventually campus borders to promote the metabolic health of the people of Hawaii and the Pacific region. The Center will leverage Hawaii’s ability to link basic science mechanisms underlying diabetes through translational research. The overall goals are to: 1) Mentor junior investigators studying DM and insulin resistance (IR), 2) Establish a Mentoring Team, 3) Develop a Resource Core that will facilitate DM and IR research, 4) Develop future investigators using a Pilot Project Program, and 5) Recruit an Associate/Full Professor with expertise in translational DM research. The global prevalence of DM continues to increase in parallel with the expanding presence of obesity and overweight adults and children. In the US, the prevalence of DM now affects 27.9 million children and adults (8.9% of US population) (http://www.diabetes.org/diabetes-basics/statistics/). Among racial and ethnic minorities, DM prevalence exceeds that of the US general population by as much as 3-fold. We have shown that among Native Hawaiians (NHs), the prevalence of DM is 22.4% with an additional 15% diagnosed with impaired glucose tolerance or pre-diabetic status. Indeed, prior epidemiological studies on DM, IR, metabolic syndrome (MetS), and heart disease risk factors among NHs and other high risk ethnic populations in Hawaii have provided a rich environment to develop this new COBRE dedicated to understanding the molecular biology underpinnings of DM, IR and the MetS. COBRE funding will be leveraged with institutional funds to accelerate the development of research excellence in DM and IR. The research focus of the Center spans the translational spectrum with one clinical study in Native Hawaiians and Pacific Islanders focused on diabetes and immunoepigenetics. While animal and cell models are being employed in three of the four studies aimed at cation channels, glucose transport in skeletal myocytes and adipocytes, and vascular calcification and dyslipidemia in diabetes and chronic kidney deficiency within the context of IR and DM. New resources being supplemented in this proposal include funding support for a Resources Core with Epigenetics, Animal Metabolic Phenotyping and Cellular Metabolism. Pilot projects are also proposed to fund 2-3 new investigators as the initial cohort of junior investigators progress towards research independence. The JABSOM leadership will also recruit an Associate/Full Professor whose research complements and focuses on translational DM and IR.