Areas of Interest
The major goal of my laboratory has been to understand basic mechanisms in the consequences and treatment of obesity, diabetes and related cardiovascular disease. Major focus has been on the role of PPAR (peroxisome proliferators-activate receptor) and mineralocorticoid (MR) transcription factors in inflammation, cell growth and cardiovascular disease (vascular and cardiac dysfunction in diabetes).
We have been determining the role of PPAR-γ in metabolic disease. We have recently used tissue specific knockout to rescue the lethal implantation defect to produce diabetic PPAR-γ null animals. Cell type specific knockouts have been produced to test the importance of tissues in the response to the clinically used PPAR-γ agonists (thiazolidinediones, antidiabetic agents). We are also investigating the role of PPAR-γ in insulin sensitization caused by the thiazolidinediones and the role of PPAR-γ in adipose tissue regrowth. The mineralocorticoid receptor (MR) is classically thought of as only regulating sodium and potassium absorption and excretion. However, its importance in cardiovascular disease has been more recently been appreciated. We are investigating the role of MR as a regulator of immune cells and inflammation. This is an exciting new area of particular clinical relevance in the use of MR antagonists in cardiovascular disease.
M.D., Cornell, 1983
Ph.D., The Rockefeller University, 1984
Duan SZ, C Ivashchenko, S Whiteshall, LG D’Alecy, C Vinson, F Gonzalez, RM Mortensen. Hypotension, lipodystrophy, and insulin resistance in generalized PPAR-gamma deficient mice rescued from embryonic lethality J Clin Invest 117 (3):812-822, 2007.
Ivashchenko C, SZ Duan, M Usher, RM Mortensen. PPAR-g knockout in pancreatic epithelial cells abolishes the inhibitory effect of Rosiglitazone on cerulein-induced acute pancreatitis. Am J Physiology 293: G319-26 2007.
Duan SZ, C Ivashchenko, Whiteshall S, LG D’Alecy, RM Mortensen. Direct and continuous measurement of pressure overload and correlation with cardiac phenotypes in mice. Physiologic Measurement 28: 1329-1339, 2007
Ye C, SZ Duan, MO Sowell, DS Milstone, RM Mortensen. Muscarinic regulation of the hyperpolarization-activated current, If, and beating rate requires Gao mediated pathways Am J Physiology 294: H979-985 2008 PMCID:PMC1963439
Gupta, D., T.L. Jetton, RM Mortensen, S.Z. Duan, M. Peshavaria, and J.L. Leahy, In vivo and in vitro studies of a functional peroxisome proliferator-activated receptor gamma response element in the mouse pdx-1 promoter. J Biol Chem, 2008. 283(47): p. 32462-70 PMCID: PMC2583321
Duan, S.Z., M.G. Usher, E.L.t. Foley, D.S. Milstone, F.C. Brosius, 3rd, and RM Mortensen, Sex dimorphic actions of rosiglitazone in generalised peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-deficient mice. Diabetologia. 2010 In press NIHMSID 209328
Usher, MG, SZ Duan, C Ivaschenko, RA.Frieler, S Berger, G Schütz, CN Lumeng, RM Mortensen. Myeloid Mineralocorticoid Receptor Controls Macrophage Polarization and Cardiovascular Hypertrophy and Remodeling in Mice. J Clin Invest (2010) 120(9): p. 3350-64.PMC Journal In Process