Lily Q. Dong, Ph.D., Associate Professor
Iowa State University
1991

(210) 567-4849
dongq@uthscsa.edu

Insulin resistance is a primary contributing factor in the pathogenesis of type 2 diabetes. This condition is characterized by the loss of insulin sensitivity in tissue, resulting in an impairment of glucose breakdown in cells, an unregulated production of glucose in hepatic cells, and a reduction of glucose uptake in skeletal muscle, resulting in a greatly increased glucose level in the bloodstream. Recently a new hormone has been identified in the human body known as adiponectin. This hormone is secreted by adipose tissue and is released into the bloodstream. The serum concentration of adiponectin is significantly reduced in type 2 diabetic and obese patients. A number of studies have shown that adiponectin is an insulin sensitizer by enhancing insulin sensitivity, which has the potential to be used therapeutically in the treatment of type 2 diabetes and obesity. However, the molecular mechanism governing adiponectin action is largely unknown.

Our research interest is focused on 1) the elucidation of the molecular pathway(s) mediating adiponectin signaling in cells, 2) the investigation of the molecular mechanism regulating adiponectin levels in the human body, and 3) the molecular mechanism of the cross-talk between Insulin signaling pathway and Adiponectin signaling pathway. We have found that APPL1, an adaptor protein with multiple function domains, is a signaling molecule immediate binding to adiponectin receptors, and positively mediate adiponectin signaling in muscle cells (Mao et al., 2006, Nat. Cell Biol., 8: 516-523). The findings from our studies will provide potential mechanisms behind insulin resistance and the development of type 2 diabetes.

Research Techniques:
Signal Transduction
Yeast two-hybrid system
Identification of novel signaling molecules and signaling pathways
Knock out mice generation

Publications:
(Publications before 1997 were under the name of Dong, Q.)

Wang, C., Mao, X., Wang, L., Liu, M., Wetzel, M., Guan, K-L, Dong, L. Q., and Liu, F. (2007).
Crosstalk between adiponectin and insulin signaling pathways: a molecular mechanism for adiponectin as an insulin sensitizer. J. Biol. Chem. 282, 7991-7996.

Wang L, Balas B, Christ-Roberts CY, Kim RY, Ramos FJ, Kikani CK, Li C, Deng C, Reyna S, Musi N, Dong LQ, DeFronzo RA, Liu F. (2007) Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo. Mol Cell Biol. Sep;27(18):6497-505. Epub 2007 Jul 9.

Li J, Mao X, Dong LQ, Liu F, Tong L. (2007) Crystal structures of the BAR-PH and PTB domains of human APPL1. Structure. May;15(5):525-33.

Mao X, Hong JY, Dong LQ. (2006) The Adiponectin Signaling Pathway as a Novel Pharmacological target. Mini Rev Med Chem. Dec;6(12):1331-40.

Riojas RA, Kikani CK, Wang C, Mao X, Zhou L, Langlais PR, Hu D, Roberts JL, Dong LQ, Liu F. (2006) Fine tuning PDK1 activity by phosphorylation at Ser163. J Biol Chem. Aug 4;281(31):21588-93. Epub 2006 Jun 2.

Ramos FJ, Langlais PR, Hu D, Dong LQ, Liu F. (2006) Grb10 mediates insulin-stimulated degradation of the insulin receptor: a mechanism of negative regulation. Am J Physiol Endocrinol Metab. Jun;290(6):E1262-6. Epub 2006 Jan 24.

Mao X, Kikani CK, Riojas RA, Langlais P, Wang L, Ramos FJ, Fang Q, Christ-Roberts CY, Hong JY, Kim RY, Liu F, Dong LQ. (2006) APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nat Cell Biol. 2006 May;8(5):516-23. Epub 2006 Apr 16. Erratum in: Nat Cell Biol. 2006 Jun;8(6):642.
High lighted article on cover page Research Highlight Commentary in Cell Metabolism 2006, 4, 5-6.

Dong LQ, and Liu F. (2005) PDK2: the missing piece in the receptor tyrosine kinase signaling pathway puzzle. Am J Physiol Endocrinol Metab. Aug;289(2):E187-196.