Shao, Jianhua, M.D., Ph.D.
Assistant Professor
Graduate Center for Nutritional Sciences

Room 583, Wethington Building
Graduate Center for Nutritional Sciences
900 S. Limestone
University of Kentucky
Lexington, KY 40536-0200
Tel: (859)-323-4933 ext 81801
Fax: (859)-257-3646
e-mail: jshao2@uky.edu

Academic Appointments:

• Graduate Center for Nutritional Sciences

Education:

• M.D., Xinxiang Medical College, P.R. China
• M.S., Endocrinology, Henan Medical University, P.R. China
• Ph.D., Endocrinology, Peking University, P.R.China
• Postdoctoral Fellow, Department of Nutrition, Case Western Reserve University
• Postdoctoral Fellow, Department of Pediatrics, University of Colorado Health    Sciences Center

Awards:

• American Diabetes Association, Thomas R. Lee Award
• American Diabetes Association, Career Development Award
• NIDDK Career Development Award
• American Diabetes Association, Junior Faculty Award
• American Diabetes Association, Travel Award, 2004 and 2006

Research interests:

The United States is experiencing an epidemic of obesity and obesity-related type 2 diabetes. From 1980 through 2002, the number of Americans with diabetes more than doubled (from 5.8 million to 13.3 million, CDC, 2004). Elucidation of the pathogenic mechanisms of obesity and diabetes is critical for the development of therapy and prevention strategies.

1. Adiponectin is an adipose-derived hormone with a relatively high concentration in circulation . Adiponectin plays an important role in regulating energy metabolism; and also has anti-inflammatory and anti-atherogenic properties. Low plasma adiponectin levels were observed in both human and animal models under the conditions of obesity and diabetes. Our study has identified the C/EBPα responding elements in the human adiponectin gene, and has demonstrated that
C/EBPα plays a key role in controlling adiponectin gene expression in adipose tissue. Our recent studies demonstrate that Foxo1 is another important transcription factor that directly increases adiponectin gene transcription through two Foxo responding elements in the proximal promoter. The studies also reveal that Foxo1 interacts with C/EBPα and forms a transcription complex in the adiponectin promotor. Furthermore, SIRT1 enhances Foxo1 and C/EBPα interaction and adiponectin gene expression. The ultimate goal of this project is to determine the molecular mechansims of diminished adiponectin gene expression in obesity and type 2 diabetes.

2. Excessive hepatic glucose production is a major contributor to hyperglycemia in both type 1 and type 2 diabetes. During the fasting, gluconeogenesis is the main component of hepatic glucose production. Hepatic gluconeogenesis is tightly regulated by hormones mainly through the transcriptional regulation of the rate-limiting enzymes, e.g. PEPCK and G-6-Pase. Although hepatic insulin resistance is the main cause of excessive hepatic glucose production in type 2 diabetes, the underlying mechanism of hepatic insulin resistance is not completely understood. This project focuses on the molecular mechanisms of hepatic insulin resistance and the consequently altered gluconeogenic enzyme gene expression in diabetes.

Selected Publications:

1. Shao, J., Catalano, P.M., Yamashita, H., Smith, S., Buyter, I., Youngren, J.F. and J.E. Friedman. Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 over-expression in skeletal muscle from obese women with Gestational Diabetes Mellitus (GDM): evidence for increased serine/theronine phosphorylation in pregnancy and GDM. Diabetes, 2000; 49:603-610.

2. Wang, L., Shao, J., Muhlenkamp, P., Liu, S., Klepcyk, P., Ren, J. and J.E. Friedman. Increased IRS-1 and enhanced skeletal muscle insulin sensitivity in mice lacking CCAAT/Enhancer-bindng Protein b (C/EBPb). Journal of Biological Chemistry, 2000; 275:14173-14181

3. Yamashita, H., Shao, J., and J.E. Friedman. Physiologic and Molecular Alterations in Carbohydrate Metabolism during Pregnancy. In: Clinical Obstetrics and Gynecology-Diabetes in Pregnancy. Edited by P. Catalano, Lippincott Press, Philadelphia, PA, 2000; 43: No. 1, 1322-1333.

4. Shao, J., Yamashita, H., Qiao, L., and J.E. Friedman. Decreased Akt kinase activity and insulin resistance in C57BL/KsJ-Leprdb/db mice. Journal of Endocrinology, 167(1): 107-115, 2000

5. Shao, J., Catalano, P.M., Yamashita, H., Ishizuka, T. and J.E. Friedman. Vanadate enhances but does not normalize glucose transport and insulin receptor phosphorylation in skeletal muscle from obese women with gestational diabetes. American Journal of Obstetrics and Gynecology, 2000; 183(5): 1263-1270

6. Yamashita, H., Shao, J., Ishizuka, T., Klepcyk, P.J., Muhlenkamp, P., Qiao, L., Hoggard, N., and J.E. Friedman. Leptin Administration Prevents Spontaneous Gestational Diabetes in Heterozygous Leprdb/+ mice: Effects on Placental Leptin and Fetal Growth. Endocrinology, 2001; 142(7):2888-2897

7. Shao, J., Yamashita, H., Qiao, L., Draznin, B., and J.E. Friedman. Phosphatidylinositol 3-Kinase Redistribution Is Associated With Skeletal Muscle Insulin Resistance in Gestational Diabetes. Diabetes, 2002; 51:19-29

8. Catalano, P. M., Nizielski, S.E., Shao, J., Preston, L., Qiao, L., and J.E. Friedman. Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes: relationship to FFA during pregnancy. Am J Physiol Endocrinol Metab. 2002;282(3):E522-33

9. Barbour L.A., Shao, J., Qiao, L., Pulawa, L.K., Jensen, D.R., Bartke, A., Draznin, B., and J.E. Friedman. Human Placental Growth Hormone Causes Severe Insulin Resistance in Transgenic Mice. American Journal of Obstetrics and Gynecology, 2002; 186(3):512-7.

10. Shao, J., and J.E. Friedman. Gestational diabetes and Maternal Insulin Resistance in the C57BLKS/J Lepr db/+ Mouse- A Unique Model for Understanding its impact on the Fetus. In: Frontiers in Animal Diabetes Research, B.F. Hansen and E. Shafrir (Ed.), Harwood Academic Press, Amsterdan, The Netherlands. 2002, 21-34

11. Yamashita, H., Shao, J., Qiao, L., and J.E. Friedman. Effects of Caloric Restriction on Spontaneous Gestational Diabetes, Insulin Sensitivity, and Fetal Growth in Heterozygous C57BLKS/J Lepr db/+ mice. Pediatrics Research. 2003; 53: 411 - 418.

12. Shao, J., Qiao, L., and J.E. Friedman. Prolactin, Progesterone, and Dexamethasone Coordinately and Adversely Regulate Glucokinase and cAMP/PDE cascades in MIN6 β Cells. Am J Physiol Endocrinol Metab. 2004; 286: E304-E310

13. L.A. Barbour, J.E. Friedman, Shao, J. , L. Qiao, W.Leitner, M. Anderson, A. Bartke, and B. Draznin. Human Placental Growth Hormone Causes Severe Insulin Resistance in Muscle by Interfering with PI 3-Kinase Insulin Signaling Pathway. Endocrinology. 2004, 145: 1144 - 1150.

14. Kirwan, J., Varastehpour, A., Jing, M., Presley, L., Shao, J., J. E. Friedman, and P. M. Catalano. Reversal of insulin resistance post-partum is linked to enhanced skeletal muscle insulin signaling. Journal of Clinical. Endocrinology and Metabolism. 2004, 89: 4678 - 4684.

15. Velliquette, R.A., Friedman, J.E., Shao, J., Zhang, B.B., and P. Ernsberger. Therapeutic Actions of an Insulin Receptor Activator and a Novel PPARγ Agonist In the SHROB Rat Model of Metabolic Syndrome X. Journal of Pharmacology and Experimental Therapeutics. 2005, 314: 422 – 430.

16. Shao, J., Qiao L, Janssen RC, Pagliassotti M, Friedman JE. Chronic Hyperglycemia Enhances PEPCK Gene Expression and Hepatocellular Glucose Production Via Elevated Liver Activating Protein/Liver Inhibitory Protein Ratio. Diabetes. 2005, 54: 976-984

17. Qiao, L. MacLean, P., Schaack, J., Orlicky, D., Darimont, C., Pagliassotti, M., Friedman, J.E. and J. Shao. C/EBPα Regulates Adiponectin Gene Transcription through an Intronic Enhancer. Diabetes. 2005, 54: 1744-1754

18. Qiao, L., Schaack, J., and J. Shao. Suppression of Adiponectin Gene Expression by Histone Deacetylase Inhibitor Valproic Acid. Endocrinology. 2006, 147(2): 865-874.

19. Qiao, L., MacLean, P., You, H., Schaack, J., and J. Shao. Knocking down Liver C/EBPα by Adenovirus-transduced Silent Interfering Ribonucleic Acid Improves Hepatic Gluconeogenesis and Lipid Homeostasis in db/db Mice. Endocrinology. 2006, 147(6): 3060-3069

20. Qiao, L. MacDougald, OA., and J. Shao. C/EBPα Mediates Induction of Hepatic Phosphoenolpyruvate Carboxykinas by p38 Mitogen-activated Protein Kinase. Journal of Biological Chemistry. 2006, 281(34):24390-24397

21. Qiao, L. and J. Shao. SIRT1 Regulates Adiponectin Gene Expression through Foxo1-C/EBPα Complex. Journal of Biological Chemistry.2006, 281(52):39915-24

22. J.M. Schroeder-Gloeckler, S.M. Rahman, R.C. Janssen, L. Qiao, J. Shao, M. Roper, et al., CCAAT/enhancer-binding protein beta (C/EBPbeta ) deletion reduces adiposity, hepatic steatosis, and diabetes in Leprdb/db mice. Journal of Biological Chemistry. 2007, 282: 15717 - 15729

23. Qiao, L., Zou, C.H., Jerome Schaack, Peter F. Johnson and J. Shao. Transcriptional Regulation of Fatty Acid Translocase/CD36 Expression by CCAAT/Enhancer-Binding Protein a. Journal of Biological Chemistry. 2008, 283(14): 8788-8795

24. Zou, C.H., and Shao, J. Role of Adipocytokines in Obesity-Associated Insulin Resistance. Journal of Nutritional Biochemistry. (In press, online)

25. Qiao, L., Zou, C.H., van der Westhuyzen, D.R., and J. Shao. Adiponectin Reduces Plasma Triglyceride by Increasing VLDL-Triglyceride Catabolism. Diabetes (in press, online)