Mouse Metabolic Phenotyping Center

Metabolic syndrome and Type 2 diabetes are devastating our health care system and compromising the quality of life for millions. These conditions have become highly prevalent because people have adopted a diet for which they are poorly adapted and a lifestyle that is largely inactive. Understanding the pathogenesis of this condition is paramount to eliminating it.  In our laboratory we seek to i) understand the pathogenesis of metabolic diseases such as obesity and diabetes, and ii) delineate means to prevent or reverse the condition.

Our goals are to define mechanisms that control (i) intrahepatic energy balance during acute perturbations, (ii) intrahepatic and whole body energy balance when modifications in diet and physical activity are employed, and (iii) site-specific regulation of muscle glucose uptake in normal physiology, in insulin resistant states induced by high fat feeding and in insulin sensitive states induced by physical exercise.

We use a variety of animal models (mostly mutant mice and rats), isotopic techniques and analytical methods that allow us to study metabolism from gene to the whole organism. In many of our studies we use physical exercise, insulin-stimulation, glucagon-stimulation or diet to challenge systems of metabolic control. The research we undertake is critical to both a basic understanding of fuel metabolism but also has important implications to diabetes, obesity and heart disease.

RECENT PUBLICATIONS

Fueger, P.T., D.P. Bracy, C. Malabanan, R.R. Pencek, and D.H. Wasserman. Distributed control of glucose uptake by working muscles of conscious mice: roles of transport and phosphorylation. Am. J. Physiol. 286: 77-84, 2004.

Fueger, P.T., S. Heikkinen, D.P. Bracy, C.M. Malabanan, M. Laakso, and D.H. Wasserman. Hexokinase II partial knockout impairs exercise-stimulated muscle glucose uptake in oxidative muscles of mice. Am. J. Physiol 285: 958-963, 2003.

Fueger, P.T., D.P. Bracy, C.M. Malabanan, R.R. Pencek, D.K. Granner, and D.H. Wasserman. Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high fat fed C57BL/6J. Diabetes 53: 306-314, 2004.

Shearer, J, D.B. Bracy, T. DePaulis, R.R. Pencek, T.E. Graham, and D.H. Wasserman. Quinides of roasted coffee increase insulin action in Conscious Rats. J. Nutr. 133: 3529-32, 2003.

Fueger, P.T., H.S. Hess, D.P.Bracy, R.R. Pencek, K.A. Posey, M.J. Charron, and D.H. Wasserman. Control of exercise-stimulated muscle glucose uptake by GLUT4 is dependent on muscle glucose phosphorylation capacity. J. Biol. Chem. 279: 50956-61, 2004.

Camacho, R.C., R.R. Pencek, D.B. Lacy, F.D. James, and D.H. Wasserman.  Suppression of endogenous glucose production by mild hyperinsulinemia during exercise is predominantly determined by portal venous insulin. Diabetes 53: 285-293, 2004.

Galassetti P, D. Tate, R.A. Neill, S. Morrey, D.H. Wasserman, and S.N. Davis. Effect of gender on the counterregulatory responses to exercise after antecedent hypoglycemia in type-1 diabetes. Am J Physiol 287: E16-24, 2004.

Shearer, J., P.T. Fueger, D.P. Bracy, J.N. Rottman, J.A. Clanton, and D.H. Wasserman. AMP Kinase-induced skeletal muscle glucose but not LCFA uptake is dependent on nitric oxide. Diabetes 53:1429-1435, 2004.

Ma, Li-Jun, S. Mao, T. Kanjanabuch, Y. Guan, Y. Zhang, Y. N.J. Brown, L.S. Swift, O.P. McGuinness, D.H. Wasserman, and A.B. Fogo, Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 53: 336-346, 2004.

Pencek, R.R., F. James, D. Lacy, R. Camacho, P. Fueger, and D.H. Wasserman. Exercise-induced changes in insulin and glucagon are not required for enhanced glucose uptake by the liver following exercise but influence the fate of glucose. Diabetes 53: 3041-3047, 2004.

Pencek, R.R., D. Battram, J. Shearer, D. Lacy, F. James, T. Graham, and D.H. Wasserman. Antagonism of hepatic adenosine receptors enhances net hepatic glucose uptake during a glucose load. J. Nutr 134:3042-6. 2004.

Fueger, P.T., H.S. Hess, D.P. Bracy, R.R. Pencek, K.A. Posey, M.J. Charron, and D.H. Wasserman. Regula­tion of insulin-stimulated muscle glucose uptake in the conscious mouse: dependence on phosphorylation capacity. Endocrinology 145:4912-6, 2004.

Shearer, J., P.T. Fueger, J.N. Rottman, D.P. Bracy, P.H. Martin, and D.H. Wasserman. AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo. Am J Physiol. 287:E871-877, 2004.

Pencek, R.R. J. Shearer, R.C. Camacho, F.D. James, D.B. Lacy, P.T. Fueger, E.P. Donahue, W. Snead, and D.H. Wasserman. 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside Causes Acute Hepatic Insulin Resistance in vivo. Diabetes, 54:355-360, 2005.

Shearer, J., P.T. Fueger, J.N. Rottman, D.P. Bracy, B. Binas, and D.H. Wasserman. Concentration-dependent and reciprocal effects of heart-type fatty acid binding protein on fatty acid and glucose utilization during exercise. Am J Physiol, 288:E292-7, 2005.

Camacho, RC, R.R. Pencek, D.B. Lacy, F.D. James, E.P Donahue, D.H. Wasserman. Portal Venous 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside infusion overcomes hyperinsulinemic suppression of endogenous glucose output. Diabetes 54: 373-382, 2005.

Fueger, P.T., J. Shearer, D.P. Bracy, C.M. Malabanan, K.A. Posey, R.R. Pencek, O.P. McGuinness, and D.H. Wasserman. Control of muscle glucose uptake: Test of the rate-limiting step paradigm in conscious, unrestrained mice. J. Physiol. ( London) 562: 925-935, 2005.

Fueger, P.T., J. Shearer, T.M. Krueger, K.A. Posey, D.P. Bracy, S. Heikkinen, M. Laakso, J.N. Rottman, and D.H. Wasserman^. Hexokinase II protein content is a determinant of exercise endurance capacity. J. Physiol. ( London) 566 (Pt 2):533-41, 2005.

Shearer, J, P.T. Fueger, D.P. Bracy, J.A. Clanton, D.H. Wasserman, and J.N. Rottman. Partial gene deletion of heart-type Fatty Acid-binding protein limits the severity of dietary-induced insulin resistance. Diabetes. 54: 3133-9, 2005.

Camacho R.C., D.B. F.D. James, E.P. Donahue, and D.H. Wasserman. 5-aminoimidazole-4-carboxamide-1-B-D-ribofuranoside renders glucose output by the liver of the dog insensitive to a pharmacological increment in insulin.  Am. J. Physiol. 289:E1039-43, 2005.

Ayala, J.E., D.P. Bracy, O.P. McGuinness, and D.H. Wasserman. Considerations in designing the hyperinsulinemic-euglycemic clamp in the conscious mouse. Diabetes 55(2):390-7, 2006.

Camacho, R.C., D.P. Donahue, F.D. James, E.D. Berglund, and D.H. Wasserman. Energy state of the liver during short term and exhaustive exercise in C57BL/6J mice. Am. J. Physiol. 290:E405-8, 2006.

Liang X., T. Kanjanabuch, S. Mao, C.M. Hao, T.W. Tang, P. Declerck, A.H. Hasty, D.H. Wasserman, A.B. Fogo, and L.J. Ma. Plasminogen activator inhibitor-1 modulates adipocyte differentiation. Am J Physiol 290:E103-E113, 2006.

Shearer, J., E.A. Sellars, A. Farah, T.E. Graham, and D.H. Wasserman. Effects of chronic coffee consumption on in vivo glucose kinetics. Can J Physiol Pharmacol. 85(8): 823-30, 2007.

Ayala J.E., D.P. Bracy, P.T. Fueger, and D.H. Wasserman. Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice. Diabetes. 56(4):1025-33, 2007.

Rao, R., O.P. McGuinness, D.H. Wasserman, and M.D. Breyer. Glycogen synthase kinase 3 inhibition improves insulin stimulated glucose metabolism but not hypertension in high fat fed C57/BL6J mice. Diabetologia 50: 452-60, 2007.

Fueger, P.T., C.Y. Li, J.E. Ayala, J. Shearer, D.P. Bracy, M.J. Charron, J.N. Rottman, and D.H. Wasserman.  Glucose kinetics and exercise tolerance in GLUT4 Null C57BL/6 mice.  J. Physiol. J. Physiol. 582(Pt 2): 801-12, 2007.

Fueger, P.T., R.S. Lee-Young, J. Shearer, D.P. Bracy, S. Heikkinen, M. Laakso, J.N. Rottman, and D.H. Wasserman.  Phosphorylation barrier to muscle glucose uptake in high fat fed mice: studies in mice with a 50% reduction in hexokinase II. Diabetes. 56(10):2476-84, 2007.

EDUCATION

B.S., University of California, Los Angeles, 1979

M.S., University of California, Los Angeles, 1981

Ph.D., University of Toronto, 1985