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

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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.