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Investigating the Molecular Link Between Obesity, Inflammation, and Type 2 Diabetes

Our research focuses on obesity, insulin resistance, and type 2 diabetes. For more than 25 years, we have made a significant contribution to the field with 143 peer-reviewed publications, mostly in high-impact scientific journals. Obesity is a major cause of type 2 diabetes, and together they impact more than 500 million people worldwide. Obesity is characterized by insulin resistance in which insulin’s ability to regulate glucose metabolism is impaired, and insulin resistance is an important early event in the development of type 2 diabetes. The goal of our NIH-funded research program is to investigate the molecular link between obesity, inflammation, and type 2 diabetes. Our current projects focus on the role of obesity-mediated inflammation in insulin resistance, and this is largely based on our earlier findings that macrophages and inflammatory cytokines regulate glucose metabolism in skeletal muscle and liver. Using novel genetic mouse models of altered macrophage function and cytokine signaling developed by our laboratory and elegant metabolic procedures, we investigate the underlying mechanism by which obesity-mediated inflammation causes insulin resistance and type 2 diabetes. Other projects focus on the therapeutic potential of anti-inflammatory cytokine as well as endoplasmic reticulum stress regulators in the treatment of insulin resistance.

Heart failure is a leading cause of mortality in type 2 diabetes, but the underlying mechanism by which diabetes increases cardiovascular events is presently unknown. Diabetic heart is characterized by altered metabolism and insulin resistance that may be causally associated with functional and pathological abnormalities. Our current projects utilize experimental mouse models of obesity (e.g., chronic high-fat diet feeding) as well as genetic mouse models of altered myocardial ER stress to determine the molecular mechanism of diabetic heart disease.

Collaboration Projects: Our research program has always fostered collaborative research. One collaborative research with a leading cancer biologist on campus examines a potential link between diabetes and cancer using genetic mouse models of breast cancer coupled to our sophisticated experimental approaches to assess energy balance and metabolism. Another collaborative research with a leading microbiome program at NYU examines a novel role of intestinal microflora in obesity and insulin resistance.

National Mouse Metabolic Phenotyping Center

The National Mouse Metabolic Phenotyping Center (MMPC) Consortium (www.mmpc.org) was established by the National Institutes of Health in 2001 to provide innovative and unique scientific approaches to the global research community. Currently, we are one of five National MMPCs awarded by the NIH to serve on this consortium with other Centers located at the Vanderbilt University, UC Davis, University of Michigan, and University of Cincinnati. The National MMPC at UMass is designed to provide an array of sophisticated and elegant research techniques to the scientific community for the purpose of investigating mouse models of human disease. Our goal is to advance medical and biological research by offering comprehensive, standardized, and high quality metabolic phenotyping tools for mouse models of obesity, diabetes, and its complications. Our Center is composed of multidisciplinary group of investigators and leading scientists with state-of-the-art technologies at the UMass Medical School. The National MMPC at UMass consists of the following Phenotyping Cores: 1) Metabolism Core performs elegant, physiological, and mostly non-invasive metabolic procedures to measure insulin sensitivity and glucose/lipid/protein metabolism, body composition, energy balance at varying temperature and light/dark cycle, and exercise effects in mice. 2) Analytical Core utilizes Luminex and Cobas Clinical Chemistry Analyzer for high-throughput and multiplexed analyses of serum/tissue levels of hormones, cytokines/chemokines, and metabolites. 3) Islet Core conducts sophisticated in vivo, ex vivo, and in vitro analyses of pancreatic function and insulin secretion in mice. 4) Cardiovascular Core applies high-frequency and high-resolution digital imaging platform with color Doppler mode to conduct echocardiography for non-invasive assessment of cardiovascular function and structure, blood pressure, and endothelial function as well as elegant micro-surgery to generate mouse models of CVD, PVD, and aneurysm to investigate diabetic complications.

Our overall mission is to find a cure for type 2 diabetes.

We are located at the 9th floor of the Albert Sherman Center, and if you are interested in visiting our research program, please contact our administrative assistant, Ms. Theresa Kane at (508) 856-6840 or theresa.kane@umassmed.edu.

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