W Timothy Garvey MD

The Garvey laboratory is interested in the molecular, metabolic, and genetic basis of type 2 diabetes mellitus, insulin resistance, and obesity. Studies involve cellular and molecular biology of cell and animal models, metabolic investigations of human subjects on a clinical research ward, and genetic epidemiology. The combined approach of human physiology, genetics, and basic cell and molecular biology provides the laboratory with a flexible and powerful capability for hypothesis testing relevant to human disease. Principal research activities include:

• Role of GLUT 4 glucose transporters and the glucose transport system in insulin resistance. This work utilizes cultured cell, animal models, and humans (in vivo metabolic studies and ex vivo studies of tissues) as model systems, and tests hypotheses relating to abnormalities in GLUT gene expression and cellular trafficking of GLUT4-containing vesicles.
• Molecular Mechanisms of Human Insulin Resistance. The laboratory systematically identifies differential gene expression in muscle and fat from insulin sensitive, insulin resistant, and Type 2 Diabetic patients using cDNA microarrays and proteomics. The contribution of selected novel genes/proteins in cell biology and metabolism is investigated using a variety of methodologies including gene hyperexpression/knock-out in cultured cells and mice.
• Molecular and Metabolic Defects Impairing Lipid Oxidation in Insulin Resistance. These studies feature application of NMR and metabolomic approaches, with a special focus on mitochondrial function, to explain defective lipid oxidation and lipid accumulation in skeletal muscle.
• Interaction between Environment and Genes in the Pathogenesis of Diabetes and Obesity and Related Metabolic Subphenotypes. These studies examine the contribution of specific gene polymorphisms (for example UCP3) to clinical and metabolic traits in relationship to environmental parameters such as diet and physical activity. Study groups include Gullah speaking African Americans and families with adolescent sib pairs discordant for obesity and/or Type 2 Diabetes.
• Pathophysiology and Clinical Diagnoses of the Insulin Resistance (or Metabolic) Syndrome. These studies include the impact of race and racial genetic admixture of the Insulin Resistance Syndrome trait cluster.
• Markers and Mechanisms of Vascular Disease in Diabetes. These studies involve secreted factors from adipocytes and gene polymorphisms, and collaborations with the DCCT/EDIC Study Group (i.e., the national cohort of DCCT/EDIC patients with Type 1 Diabetes) and the VA Diabetes Study (i.e., a VA cooperative study in Type 2 Diabetic patients).