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Rubinow, Katya 2

Katya Rubinow, M.D.

Metabolism, Endocrinology & Nutrition

Assistant Professor of Medicine


Focus

My research focus is the role of sex steroid signaling in macrophage biology, specifically in the setting of cardiometabolic disease. Aging in men is characterized by progressive decline in testosterone production, and very low levels of circulating androgens consistently have been associated with increased risk of insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Further, IR and T2DM tend to arise prior to CVD in these men and may contribute substantially to cardiovascular risk. Consequently, determining the physiologic effects of testosterone on systemic insulin sensitivity could have clinical relevance to all men as they age and offer novel therapeutic strategies for preventing or delaying diabetes and CVD.


Clinical Interest

Dr. Rubinow sees patients at the Wednesday Endocrinology Clinic at Harborview Medical Center.


Research Interest

My research focus is the role of sex steroid signaling in macrophage biology, specifically in the setting of cardiometabolic disease.  Aging in men is characterized by progressive decline in testosterone production, and very low levels of circulating androgens consistently have been associated with increased risk of insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD).  Further, IR and T2DM tend to arise prior to CVD in these men and may contribute substantially to cardiovascular risk.  Consequently, determining the physiologic effects of testosterone on systemic insulin sensitivity could have clinical relevance to all men as they age and offer novel therapeutic strategies for preventing or delaying diabetes and CVD.

In both human and animal models, IR and T2DM are associated with elevated levels of macrophage-derived cytokines and increased adipose tissue infiltration by macrophages.  Inflammatory cytokines secreted by macrophages directly can inhibit insulin signaling in adipocytes and may contribute to systemic IR.  Furthermore, in mouse models, interventions that alter the phenotype of adipose tissue macrophages (ATMs) can potentiate changes in systemic insulin sensitivity.  Macrophages express the androgen receptor (AR), and AR signaling in macrophages affects cytokine generation.  Thus, AR signaling in macrophages could contribute to the maintenance of insulin sensitivity in men.  My research is dedicated to investigating the effects of differential sex steroid signaling on macrophage biology and attendant changes in systemic insulin sensitivity.



Publications

Rubinow KB, Tang C, Hoofnagle AN, Snyder CN, Amory JK, Heinecke JW, and Page ST. (2011) Acute sex steroid withdrawal increases cholesterol efflux capacity and HDL-associated clusterin in men. Steroids, in press.

Rubinow KB, Snyder CN, Amory JK, Hoofnagle AN, and Page ST. (2011) Acute testosterone  deprivation reduces insulin sensitivity in men. Clin Endocrin (Oxf), in press. Epub 8/1/2011

Lee A, Rubinow KB, Roth M, Bremner WJ, Page ST, and Amory JK. (2011)  Pharmacokinetics of modified slow-release oral testosterone over nine days in normal men with experimental hypogonadism. J. Androl, in press

Rubinow KB, Amory JK, and Page ST. (2011) Androgens exert sexually dimorphic effects on angiogenesis: novel insight into the relationship between androgens and cardiovascular disease. Asian J Androl 13: 626-7.

Rubinow KB and Hirsch IB. (2011) Reexamining metrics for glucose control. JAMA 305:1132-   3.

Shansky RM, Rubinow K, Brennan A, and Arsten AF. (2006) The effects of sex and hormonal  status on restraint stress-induced working memory impairment. Behav Brain Funct 2:8.