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Jason Kim, PhD

Our research investigates obesity, diabetes, and cardiovascular complications using elegant metabolic and molecular procedures and transgenic mouse models of altered metabolism. Our NIH-funded program examines the role of inflammation and macrophages in obesity-mediated insulin resistance. As a National Mouse Metabolic Phenotyping Center, we collaborate with leading academic investigators to define the molecular link between obesity and type 2 diabetes and further work with pharmaceutical industries to identify new therapeutic approaches to treat metabolic disease. The goal of our research is to understand how obesity causes diabetes and to find its cure.

Role of inflammation in obesity, diabetes, and cardiovascular complications

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 define the molecular link between obesity, insulin resistance, and type 2 diabetes. Our current projects focus on the role of obesity-mediated inflammation in insulin resistance and are 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 as well as experimental models of obesity (chronic feeding of high-fat diet, leptin deficiency), we investigate the underlying mechanism by which obesity-mediated inflammation causes insulin resistance and type 2 diabetes.

Heart failures is a leading cause of mortality in 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 precede functional and pathological abnormalities. Based on our earlier findings that local inflammation develops in obese and diabetic heart, the goal of our NIH-funded research program is to understand the role of inflammation and macrophages in diabetic heart disease.

National Mouse Metabolic Phenotyping Center at UMass

The UMass Mouse Metabolic Phenotyping Center (MMPC) is one of five NIH-funded National MMPC Consortium (www.mmpc.org) and involves a multidisciplinary group of investigators at UMass Medical School who perform an array of novel and sophisticated metabolic, analytical, and functional experiments using state-of-the-art equipment for the purpose of investigating transgenic mouse useful for understanding obesity, diabetes and its complications. The goal of the UMass MMPC is to provide comprehensive metabolic and functional characterization of transgenic mice using unique and standardized techniques mostly involving in vivo and physiological setting that are complemented by analytical experiments using serum/tissue samples and measure of islet and cardiovascular function in mice.

The UMass MMPC consists of the following Cores: 1) Metabolism Core applies elegant hyperinsulinemic-euglycemic clamp to measure insulin action and glucose metabolism in individual organs, hyperglycemic clamp to assess pancreatic b-cell function in awake mice, metabolic cages to measure energy expenditure, food intake, and physical activity, 1H-MRS to assess body composition, exercise studies using treadmill, and drug trial studies.  2) Analytical Core uses Luminex and Cobas Clinical Chemistry Analyzer to provide a high-throughput and multiplexed measurement of serum/tissue levels of hormones, cytokines, and metabolites, and performs molecular experiments to determine insulin/metabolic/inflammatory signaling.  3) Islet Core performs elegant islet isolation and ex vivo and in vitro analysis of islet function and histology, and molecular analysis.  4) Cardiovascular Core uses state-of-the-art Vevo2100 In Vivo Imaging System to conduct echocardiography and tissue Doppler imaging for cardiac structure/function analyses, vascular/endothelial function, and surgical models of cardiovascular diseases.  5) Humanized Mouse Cell Transplantation and Assessment Core provides humanized mice and elegant technique to assess in vivo function of transplanted human islets and stem cell-derived b-cells in immunodeficient mice.

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