Endocrinology, Diabetes and Hypertension

Brian W. Kim, M.D.

The primary goal of Dr. Kim’s research is to understand the physiologic role or roles of the type 2 deiodinase  (D2) in human skeletal muscle.   D2 activates thyroid hormone in the cytoplasm, providing activated thyroid hormone for the nucleus.  Given this mechanism, it is unsurprising that D2 has been found to be a major determinant of thyroid hormone action in the pituitary gland, as well as in brown adipose tissue.  The hypothesis I am testing is that D2 is a major determinant of thyroid hormone action in human skeletal muscle as well.  If this hypothesis is correct, the implication would be that D2 may be an important modulator of energy expenditure, glucose homeostasis, and other metabolic processes that are sensitive to thyroid hormone in skeletal muscle.  Because the thyroid hormone inactivating type 3 deiodinase (D3) is induced in skeletal muscle under conditions of critical illness, a setting in which D2 activity is lost, I am also interested in understanding what factors regulate D3 expression in muscle cells.

 Selected References:

1. Carvalho-Bianco SD, Kim BW, Zhang JX, et al. 2004 Chronic cardiac-specific thyrotoxicosis increases myocardial beta-adrenergic responsiveness. ME 18:1840-9
2. Dentice M, Bandyopadhyay A, Gereben B, et al. 2005 The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. Nat Cell Biol 7:698-705
3. Huang SA, Mulcahey MA, Crescenzi A, et al. 2005 TGF-{beta} promotes inactivation of extracellular thyroid hormones via transcriptional stimulation of type 3 iodothyronine deiodinase. ME Epub ahead of print.
4. Maia AL, Kim BW, Huang SA, Harney JW, Larsen PR 2005 Type 2 iodothyronine deiodinase is the major source of plasma T(3) in euthyroid humans. JCI 115:2524-33
5. Watanabe M, Houten S, M C, et al. 2005 Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature in press