Role of inflammation in obesity, diabetes and cardiovascular complications

Type 2 diabetes is the most common metabolic disease in the world and affects more than 250 million people. It is characterized by insulin resistance in which insulin's ability to regulate glucose metabolism is impaired. Obesity is a major risk factor for type 2 diabetes, and the goal of our research is to understand the molecular mechanism by which obesity causes insulin resistance. We believe that inflammation plays an important role in this process, and circulating levels of inflammatory cytokines are elevated in obese, diabetic subjects. Our recent study showed that pro-inflammatory cytokine, IL-6, causes insulin resistance, whereas treatment with anti-inflammatory cytokine, IL-10, protects mice from developing diabetes. These effects are associated with macrophage infiltration in adipose tissue and skeletal muscle, and alterations in insulin signaling pathway. Using experimental model of obesity (with chronic feeding of high-fat diet), genetic model of obesity (RCS10, TallyHo mice), and transgenic mice with altered cytokine expression (MCK-IL10, IL-6 KO mice), our research funded by the NIH and the American Diabetes Association investigates the role of inflammation in obesity and insulin resistance.

Heart failure is the leading cause of mortality in diabetes, but the mechanism by which diabetes increases cardiovascular events is presently unknown. Diabetic heart is characterized by altered metabolism and insulin resistance, which may precede functional and pathological changes and therefore play an important role in diabetic heart failure. We have previously shown that chronic high-fat feeding impairs myocardial glucose metabolism, and this was associated with ventricular hypertrophy and cardiac dysfunction in obese mice. Our recent study found that local inflammation is activated in heart under obese condition, and this leads to suppression of AMP-activated protein kinase, which is a critical sensor of energy utilization in heart. Our research funded by the American Heart Association investigates the role of nutrient stress and inflammation in the pathogenesis of diabetic heart failure.

UMass Mouse Phenotyping Center

The UMass Mouse Phenotyping Center (UMPC; http://umassmed.edu/umpc) is a core facility involving a multidisciplinary group of investigators at the University of Massachusetts Medical School, and performs an array of elegant and standardized experiments using state-of-the-art instruments for the purpose of investigating transgenic mouse models of human diseases including diabetes and its complications. The goal of the UMPC is to provide comprehensive characterization of transgenic mice that are developed by academic and non-academic investigators in joint efforts to understand the etiology of human disease, and to find its cure. The UMPC consists of the following Phenotyping Cores: 1) the Metabolism Core performs sophisticated metabolic experiments to assess insulin sensitivity, glucose/lipid/protein metabolism, pancreatic function, body composition, and energy balance in mice, 2) the Analytical Core utilizes Luminex and clinical chemistry analyzer to perform a high-throughput measurement of serum/tissue levels of hormones, cytokines and metabolites known to affect metabolism, 3) the Cardiovascular Core applies a state-of-the-art imaging platform to non-invasively assess cardiac structure and function and vascular imaging to examine cardiovascular diseases associated with diabetes, and 4) the Retinopathy Core performs non-invasive and high-quality 3-D imaging of retina using funduscope and optical CT to investigate visual abnormalities associated with diabetes.