Daryl K. Granner , M.D.
Professor of Molecular Physiology and Biophysics, Emeritus

Lab Url: http://www.mc.vanderbilt.edu/root/vumc.php?site=granner

Phone Number: 615-322-7004

Email Address: daryl.granner@vanderbilt.edu

Granner, Daryl's picture

Office Address   Mailing Address

707 Light Hall

707 Light Hall 0615


Research Keywords
Insulin Action, Glucocorticoids, Gene Transcription, Hormone Response Elements, Insulin Resistance, Diabetes Mellitus

Research Specialty
Hormonal regulation of gene expression

Research Description
Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes a rate-controlling step of gluconeogenesis, the process by which cells synthesize glucose from metabolic precursors. The blood glucose level is maintained within well-defined limits in part due to precise regulation of PEPCK gene expression. To emphasize the importance of PEPCK in glucose homeostasis, over expression of this enzyme in mice results in symptoms of type II diabetes mellitus, by far the most common form of diabetes in humans. Due to the importance of blood glucose homeostasis, a number of hormones regulate a set of genes (including PEPCK) in the liver that modulate the rate of glucose synthesis. The Granner laboratory has long been interested in the multihormonal regulation of the PEPCK gene, and has worked out many of the molecular mechanisms by which hormones affect gene expression. In general, hormones regulate the transcription of genes by influencing proteins (trans-acting factors) that bind to DNA elements (cis-elements) located in the promoter, near the beginning of a gene's coding sequence. Glucocorticoids, glucagon and retinoic acid all stimulate transcription of the PEPCK gene, while insulin acts to turn off the PEPCK gene, even if the gene is stimulated by other hormones.

Our lab has characterized several cis-elements (and the trans- acting factors that bind them) that are responsible for the various hormonal responses. The collection of DNA elements and associated transcription factors is called a hormone response unit (HRU). Noteworthy is the fact that some HRUs share common DNA elements, although they bind different transcription factors. This arrangement provides for the fine-tuning of PEPCK gene regulation through a versatile mechanism that provides for additivity, synergism, redundancy, dominant repression.

Rotation, thesis and postdoctoral projects concern how these hormones individually, and collectively, regulate the rate of transcription of this important gene. Emphasis is placed on how faculty regulation of this gene could contribute to the pathophysiology of diabetes.
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Publications
Hall, RK, Wang, XL, George, L, Koch, SR, Granner, DK. Insulin represses phosphoenolpyruvate carboxykinase gene transcription by causing the rapid disruption of an active transcription complex: a potential epigenetic effect. Mol Endocrinol, 21(2), 550-63, 2007.

Whitesell, RR, Ardehali, H, Beechem, JM, Powers, AC, Van der Meer, W, Perriott, LM, Granner, DK. Compartmentalization of transport and phosphorylation of glucose in a hepatoma cell line. Biochem J, 386(Pt 2), 245-53, 2005.

Fueger, Patrick T, Bracy, Deanna P, Malabanan, Carlo M, Pencek, R Richard, Granner, Daryl K, Wasserman, David H. Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high-fat-fed C57BL/6J mice. Diabetes, 53(2), 306-14, 2004.

Herzog, B, Hall, RK, Wang, XL, Waltner-Law, M, Granner, DK. Peroxisome proliferator-activated receptor gamma coactivator-1alpha, as a transcription amplifier, is not essential for basal and hormone-induced phosphoenolpyruvate carboxykinase gene expression. Mol Endocrinol, 18(4), 807-19, 2004.

Herzog, Birger, Hall, Robert K., Wang, Xiaohui, Waltner-Law, Mary, Granner, Daryl K.. PGC-1{alpha}, As A Transcription Amplifier, Is Not Essential for Basal and Hormone-Induced PEPCK Gene Expression. Mol Endocrinol, , , 2004.

Wang, XL, Herzog, B, Waltner-Law, M, Hall, RK, Shiota, M, Granner, DK. The synergistic effect of dexamethasone and all-trans-retinoic acid on hepatic phosphoenolpyruvate carboxykinase gene expression involves the coactivator p300. J Biol Chem, 279(33), 34191-200, 2004.

Waltner-Law, M.E., Duong, David T., Daniels, Marc C. , Herzog, Birger, Wang, Xiaohui L., Prasad, Ratna and Granner, Darl K. Elements of the Glucocorticoid and Retinoic Acid Response Units are Involved in cAMP-Mediated Expression of the PEPCK Gene. J. Biol. Chem., 278, 10427-10435, 2003.

Waltner-Law, Mary, Duong, David T, Daniels, Marc C, Herzog, Birger, Wang, Xiaohui L, Prasad, Ratna, Granner, Daryl K. Elements of the glucocorticoid and retinoic acid response units are involved in cAMP-mediated expression of the PEPCK gene. J Biol Chem, 278(12), 10427-35, 2003.

Whitesell, Richard R, Ardehali, Hossein, Printz, Richard L, Beechem, Joseph M, Knobel, Susan M, Piston, David W, Granner, Daryl K, Van Der Meer, Wieb, Perriott, Laureta M, May, James M. Control of glucose phosphorylation in L6 myotubes by compartmentalization, hexokinase, and glucose transport. Biochem J, 370(Pt 1), 47-56, 2003.

Duong, D.T., Waltner-Law, M., Sears, R., Sealy, L. and Granner, D.K. Insulin Inhibits Hepatocellular Glucose Production by Disrupting the Association of CBP and RNA Polymerase II with the PEPCK Gene Promoter. J. Biol. Chem., 277, 32234-32242, 2002.

Duong, David T, Waltner-Law, Mary E, Sears, Rosalie, Sealy, Linda, Granner, Daryl K. Insulin inhibits hepatocellular glucose production by utilizing liver-enriched transcriptional inhibitory protein to disrupt the association of CREB-binding protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem, 277(35), 32234-42, 2002.

Kucera, T., Waltner-Law, M., Scott, D.K., Prasad, R. and Granner, D.K. A Point Mutation of the AF2 Transactivation Domain of the Glucocorticoid Receptor Disrupts Its Interaction with Steroid Receptor Coactivator 1. J. Biol. Chem., 277, 26098-26102, 2002.

Kucera, Tomas, Waltner-Law, Mary, Scott, Donald K, Prasad, Ratna, Granner, Daryl K. A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1. J Biol Chem, 277(29), 26098-102, 2002.

Onuma, H., Osawa, H., Yamada, K., Ogura, T., Tanabe, F., Granner, d.K. and Makino, H. Identification of the Insulin-Regulated Interaction of Phosphodiesterase 3b with 14-3-3b Protein. Diabetes, 51, 3362-3367, 2002.

Waltner-Law, M.E., Wang, X.L., Law, B.K., Hall, R.K., Nawano, M. and Granner, D.K. Epigallocatechin Gallate, a Constituent of Green Tea, Acts Like Insulin to Repress Hepatic Glucose Production. J. Biol. Chem., 277, 34933-34940, 2002.

Waltner-Law, Mary E, Wang, Xiaohui L, Law, Brian K, Hall, Robert K, Nawano, Masao, Granner, Daryl K. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem, 277(38), 34933-40, 2002.

Stafford, J.M., Wilkinson, J.C., Beechem, J.M. and Granner, D.K. Accessory Factors Facilitate the Binding of glucocorticoid Receptor to the PEPCK Gene Promoter. J. Biol. Chem., 276:39885-39891, 2001.

Cusi, K.J., Pratipanawatr, T., Koval, J., Printz, R., Ardehali, H., Granner, D.K., DeFronzo, R.A. and Mandarino, L.J. Defective Regulation of Hexokinase II Expression by Exercise in Obesity and Type 2 Diabetes. Metabolism, 5(50), 602-6, 2001.

Monroy, Alexandra M., Ruhl, Donald D., Xu, Xiequn, Granner, Daryl K., Yaciuk, Peter and Chrivia, John C. Regulation of CREB-Medicated Transcription by the SNF2/SWI-Related Protein, SRCAP. J. Biol. Chem, 276, 40721-40726, 2001.

Perriott, L.M., Kono, T., Whitesell, R.R., Knobel, S., Piston, D., Granner, D.K., Powers, A.C. and May, J.M. Glucose Uptake and Metabolism by Cultured Human Skeletal Muscle Cells: Rate-Limiting Steps. Am. J. Physiol, 281(1), E72-80, 2001.

Perriott, LM, Kono, T, Whitesell, RR, Knobel, SM, Piston, DW, Granner, DK, Powers, AC, May, JM. Glucose uptake and metabolism by cultured human skeletal muscle cells: rate-limiting steps. Am J Physiol Endocrinol Metab, 281(1), E72-80, 2001.

Stafford, JM, Waltner-Law, M, Granner, DK. Role of accessory factors and steroid receptor coactivator 1 in the regulation of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. J Biol Chem, 276(6), 3811-9, 2001.

Stafford, JM, Wilkinson, JC, Beechem, JM, Granner, DK. Accessory factors facilitate the binding of glucocorticoid receptor to the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem, 276(43), 39885-91, 2001.

Yoon, J.C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C.R., Granner, D.K., Newgard, C.B. and Spiegelman, B.M. Control of Hepatic Gluconeogenesis Through the Transcriptional Coactivator PGC-1. Nature, 413, 131-138, 2001.

Hall, R.K., Yamasaki, T., Kucera, T., Waltner-Law, M., O'Brien, R., and Granner, D.K. Regulation of Phosphoenolpyruvate Carboxykinas eand Insulin-Like Growth Factor Binging Protein ?1 Gene Expression by Insulin. J. Biol. Chem., 275, 30169-30175, 2000.

Hall, RK, Yamasaki, T, Kucera, T, Waltner-Law, M, O''Brien, R, Granner, DK. Regulation of phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein-1 gene expression by insulin. The role of winged helix/forkhead proteins. J Biol Chem, 275(39), 30169-75, 2000.

Halseth, A.E., O'Doherty, R.M., Printz, R.L., Bracy, D.P., Granner, D.K., and Wasserman, D.H. Role of Ca2+ Fluctuations in L6 Myotubes in the Regulation of the Hexokinase II Gene. J. Appl. Physiol., 88, 669-673, 2000.

Halseth, AE, O''Doherty, RM, Printz, RL, Bracy, DP, Granner, DK, Wasserman, DH. Role of Ca(2+) fluctuations in L6 myotubes in the regulation of the hexokinase II gene. J Appl Physiol, 88(2), 669-73, 2000.

Herzog, B., Waltner-Law, M., Scott, D.K., Eshrich, K. and Granner, D.K. Characterisation of the Human Liver Fructose-1,6-Bisphosphatase Gene Promoter. Biochem. J., 351, 385-392, 2000.

Rucktaschel, A.K., Granner, D.K. and Christ, B. Regulation by Glucagon (cAMP) and Insulin of the Promoter of the Human Phosphoenolpyruvate Carboxykinase Gene (Cytosolic) in Cultured Rat Hepatocytes and in Human Hepatoblastoma Cells. Biochem. J., 352, 211-7, 2000.

Stafford, J.M., Waltner-Law, M. and Granner, D.K. Role of Accessory Factors and Steroid Receptor Coactivator 1 in the Regulation of Phosphoenolpyruvate Carboxykinase Gene Transcription by Glucocorticoid. J. Biol. Chem., 276, 3811-3819, 2000.

Stafford, J.M., Wang, J.-C., Scott, D.K., Sugiyama, T., and Granner, D.K. Chapter V: HNF4 as a Liver Gene Transcription Factor. Frontiers in Diabetes, 15, 235-250, 2000.

Sugiyama, T, Wang, JC, Scott, DK, Granner, DK. Transcription activation by the orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI). Definition of the domain involved in the glucocorticoid response of the phosphoenolpyruvate carboxykinase gene. J Biol Chem, 275(5), 3446-54, 2000.

Sugiyama, T., Wang, J.-C., Scott, D.K. and Granner, D.K. Transcription Activation by the Orphan Nuclear Receptor, Chicken Ovalbumin Upstream Promoter-Transcription Factor I (COUP-TFI). J. Biol. Chem., 275, 3446- 3454, 2000.

Waltner-Law, M, Daniels, MC, Sutherland, C, Granner, DK. NF-kappa B inhibits glucocorticoid and cAMP-mediated expression of the phosphoenolpyruvate carboxykinase gene. J Biol Chem, 275(41), 31847-56, 2000.

Waltner-Law, M., Daniels, M.C., Sutherland, C. and Granner, D.K. NF-_B Inhibits Glucocorticoid and cAMP-Mediated Expression of the PEPCK Gene. J. Biol. Chem., 275, 31847-31856, 2000.

Wang, J.-C., Stafford, J.M., Scott, D.K., Sutherland, C., Granner, D.K. The Molecular Physiology of Hepatic Nuclear Factor 3 (HNF3) in the Regulation of Gluconeogenesis. J. Biol. Chem., 275, 14717-14721, 2000.

Wang, J.-C., Waltner-Law, M., Yamada, K., Osawa, H., Stifani, S. and Granner, D.K. Transducin-Like Enhancer of Split Proteins, the Human Homologs of Drosophila Groucho, Interact with Hepatic Nuclear Factor 3. J. Biol. Chem., 275, 18418-18423, 2000.

Wang, JC, Stafford, JM, Scott, DK, Sutherland, C, Granner, DK. The molecular physiology of hepatic nuclear factor 3 in the regulation of gluconeogenesis. J Biol Chem, 275(19), 14717-21, 2000.

Wang, JC, Waltner-Law, M, Yamada, K, Osawa, H, Stifani, S, Granner, DK. Transducin-like enhancer of split proteins, the human homologs of Drosophila groucho, interact with hepatic nuclear factor 3beta. J Biol Chem, 275(24), 18418-23, 2000.

Yamada, K., Printz, R.L., Osawa, H. and Granner, D.K. Human ZHX1: Cloning, chromosomal location and interaction with transcription factor NF-Y. Biochem. Biophys. Res. Commun., 261:614-621, 1999.

Ardehali, H, Printz, RL, Whitesell, RR, May, JM, Granner, DK. Functional interaction between the N- and C-terminal halves of human hexokinase II. J Biol Chem, 274(23), 15986-9, 1999.

Ardehali, H., Printz, R.L., Whitesell, R.R., May, J.M. and Granner, D.K. Functional Interaction between the Amino- and Carboxyl-Terminal Halves of Human Hexokinase II. J. Biol. Chem, 274, 15986-15989, 1999.

Hall, RK, Granner, DK. Insulin regulates expression of metabolic genes through divergent signaling pathways. J Basic Clin Physiol Pharmacol, 10(2), 119-33, 1999.

Kotani, K., Ogawa, W., Hino, Y., Kitamura, T., Ueno, H., Sano, W., Sutherland, C., Granner, D. and Kasuga, M. Dominant negative forms of Akt (protein kianse B) and atypical protein kinase Cl do not prevent insulin inhibition of phosphoenolpyruvate carboxykinase gene transcription. J. Biol. Chem., 274, 21305-21312, 1999.

Pierreux, C.E., Stafford, J., Demonte, D., Scott, D.K., Vandenhaute, J., O'Brien, R.M., Granner, D.K., Rousseau, G.G. and Lemaigre, F.P. Antiglucocorticoid activity of hepatocyte nuclear factor-6. Proc. Natl. Acad. Sci. USA, 96, 8961-8966, 1999.

Wang, J.-C., Stromstedt, P.-E., Sugiyama, T. and Granner, D.K. The Phosphoenolpyruvate Carboxykinase Gene Glucocorticoid Response Unit. Identification of the Functional Domains of Accessory Factors HNF3 and HNF4 and the Necessity of Proper Alignment of Their Cognate Binding Sites. Mol. Endocrinol., 13, 604-618, 1999.

Wang, JC, Str??mstedt, PE, Sugiyama, T, Granner, DK. The phosphoenolpyruvate carboxykinase gene glucocorticoid response unit: identification of the functional domains of accessory factors HNF3 beta (hepatic nuclear factor-3 beta) and HNF4 and the necessity of proper alignment of their cognate binding sites. Mol Endocrinol, 13(4), 604-18, 1999.

Williams, C.P., Postic, C., Robin, D., Robin, P., Parrinello, J., Shelton, K., Printz, R.L., Magnuson, M.A., Granner, D.K., Forest, C. and Chalkley, R. Isolation and Characterization of the Mouse Cytosolic Phosphoenolpyruvate Carboxykinase (GTP) Gene: Evidence for Tissue- Specific Hypersensitive Sites. Mol. Cell. Endocrinol., 148, 67-77, 1999.

Williams, CP, Postic, C, Robin, D, Robin, P, Parrinello, J, Shelton, K, Printz, RL, Magnuson, MA, Granner, DK, Forest, C, Chalkley, R. Isolation and characterization of the mouse cytosolic phosphoenolpyruvate carboxykinase (GTP) gene: evidence for tissue-specific hypersensitive sites. Mol Cell Endocrinol, 148(1-2), 67-77, 1999.

Yamada, K, Duong, DT, Scott, DK, Wang, JC, Granner, DK. CCAAT/enhancer-binding protein beta is an accessory factor for the glucocorticoid response from the cAMP response element in the rat phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem, 274(9), 5880-7, 1999.

Yamada, K, Printz, RL, Osawa, H, Granner, DK. Human ZHX1: cloning, chromosomal location, and interaction with transcription factor NF-Y. Biochem Biophys Res Commun, 261(3), 614-21, 1999.

Yamada, K., Duong, D.T., Scott, D.K., Wang, J.-C. and Granner, D.K. CCAAT/Enhancer-Binding Protein is an Accessory Factor for the Glucocorticoid Response from the cAMP Response Element in the Rat Phosphoenolpyruvate Carboxykinase Gene Promoter. J. Biol. Chem., 274, 5880-5887, 1999.

Yamada, K., Osawa, H. and Granner, D.K. Identification of proteins that interact with NF-YA. FEBS Letters, 460, 41-45, 1999.

Vogt, C., Yki-Jarvinen, H., Iozzo, P., Pipek, R., Pendergrass, M., Koval, J., Ardehali, H., Printz, R., Granner, D., DeFronzo, R. and Mandarino, L. Effects of Insulin on Subcellular Localization of Hexokinase II in Human Skeletal Muscle in Vivo. J. Clin. Endo. Metab., 83:230-234, 1998.

Koval, J.A., DeFronzo, R.A., O?Doherty, R.M., Printz, R., Ardehali, H., Granner, D.K. and Mandarino, L.J. Regulation of Hexokinase II Activity and Expression in Human Muscle by Moderate Exercise. Am. J.Physiol., 274, E304-E308, 1998.

O''Doherty, RM, Halseth, AE, Granner, DK, Bracy, DP, Wasserman, DH. Analysis of insulin-stimulated skeletal muscle glucose uptake in conscious rat using isotopic glucose analogs. Am J Physiol, 274(2 Pt 1), E287-96, 1998.

O'Doherty, R.M., Halseth, A.E., Granner, D.K., Bracy, D.P. and Wasserman, D.H. Analysis of Insulin-Stimulated Skeletal Muscle Glucose Uptake in the Conscious Rat Using Isotopic Glucose Analogues. Am. J. Physiol, 274, E287-E296, 1998.

Scott, D.K., O'Doherty, R.M., Stafford, J.M., Newgard, C.B. and Granner, D.K. The Repression of Hormone-Activated PEPCK Gene Expression by Glucose is Insulin-Independent But Requires Glucose Metabolism. J. Biol. Chem, 273, 24145-24151, 1998.

Scott, D.K., O?Doherty, R.M., Stafford, J.M., Newgard, C.B. and Granner, D.K. The Repression of Hormone-Activated PEPCK Gene Expression by Glucose is Insulin-Independent But Requires Glucose Metabolism. J. Biol. Chem, 273, 24145-24151, 1998.

Scott, D.K., Stromstedt, P.-E., Wang, J.-C. and Granner, D.K. Further Characterization of the Glucocorticoid Response Unit in the Phosphoenolpyruvate Carboxykinase Gene The Role of the Glucocorticoid Receptor-Binding Sites. Mol. Endo., , 482-491, 1998.

Scott, D.K., Stromstedt, P.-E., Wang, J.-C. and Granner, D.K. Further Characterization of the Glucocorticoid Response Unit in the Phosphoenolpyruvate Carboxykinase Gene. The Role of the Glucocorticoid Receptor-Binding Sites. Mol. Endocrinol, , 482-491, 1998.

Scott, DK, O''Doherty, RM, Stafford, JM, Newgard, CB, Granner, DK. The repression of hormone-activated PEPCK gene expression by glucose is insulin-independent but requires glucose metabolism. J Biol Chem, 273(37), 24145-51, 1998.

Scott, DK, Str??mstedt, PE, Wang, JC, Granner, DK. Further characterization of the glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene. The role of the glucocorticoid receptor-binding sites. Mol Endocrinol, 12(4), 482-91, 1998.

Sugiyama, T, Scott, DK, Wang, JC, Granner, DK. Structural requirements of the glucocorticoid and retinoic acid response units in the phosphoenolpyruvate carboxykinase gene promoter. Mol Endocrinol, 12(10), 1487-98, 1998.

Sugiyama, T., Scott, D.K., Wang, J.-C. and Granner, D.K. Structural Requirements of the Glucocorticoid and Retinoic Acid Response Units in the Phosphoenolpyruvate Carboxykinase Gene Promoter. Mol. Endo., 12, 1487-1498, 1998.

Sugiyama, T., Scott, D.K., Wang, J.-C. and Granner, D.K. Structural Requirements of the Glucocorticoid and Retinoic Acid Response Units in the Phosphoenolpyruvate Carboxykinase Gene Promoter. Mol. Endocrinol, 12, 1487-1498, 1998.

Sutherland, C, Waltner-Law, M, Gnudi, L, Kahn, BB, Granner, DK. Activation of the ras mitogen-activated protein kinase-ribosomal protein kinase pathway is not required for the repression of phosphoenolpyruvate carboxykinase gene transcription by insulin. J Biol Chem, 273(6), 3198-204, 1998.

Sutherland, C., Waltner-Law, M., Gnudi, L., Kahn, B.B. and Granner, D.K. Activation of the Ras Mitogen-activated Protein Kinase-Ribosomal Protein Kinase Pathway Is Not Required for the Repression of Phosphoenolpyruvate Carboxykinase Gene Transcription by Insulin. J. Biol. Chem, 273, 3198-3204, 1998.

Wang, J.-C., Stafford, J.M. and Granner, D.K. SRC-1 and GRIP1 Coactivate Transcriptionwith Hepatocyte Nuclear Factor 4. J. Biol. Chem., 273, 30847-30850, 1998.

Wang, JC, Stafford, JM, Granner, DK. SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. J Biol Chem, 273(47), 30847-50, 1998.

Yamada, K, Wang, JC, Osawa, H, Scott, DK, Granner, DK. Efficient large-scale transformation of yeast. Biotechniques, 24(4), 596-8, 600, 1998.

Printz, R.L., Osawa, H., Ardehali, H., Koch, S. and Granner, D.K. Hexokinase II Gene: Structure, Regulation and Promoter Organization. Biochem. Soc. Trans., 25, 107-112, 1997.

Printz, RL, Osawa, H, Ardehali, H, Koch, S, Granner, DK. Hexokinase II gene: structure, regulation and promoter organization. Biochem Soc Trans, 25(1), 107-12, 1997.

Sutherland, C, Tebbey, PW, Granner, DK. Oxidative and chemical stress mimic insulin by selectively inhibiting the expression of phosphoenolpyruvate carboxykinase in hepatoma cells. Diabetes, 46(1), 17-22, 1997.

Sutherland, C., Tebbey, P.W. and Granner, D.K. Oxidative and Chemical Stress Mimic Insulin by Selectively Inhibiting the Expression of Phosphoenolpyruvate Carboxykinase in Hepatoma Cells. Diabetes, 46, 17-22, 1997.

Ardehali, H, Tiller, GE, Printz, RL, Mochizuki, H, Prochazka, M, Granner, DK. A novel (TA)n polymorphism in the hexokinase II gene: application to noninsulin-dependent diabetes mellitus in the Pima Indians. Hum Genet, 97(4), 482-5, 1996.

Ardehali, H, Yano, Y, Printz, RL, Koch, S, Whitesell, RR, May, JM, Granner, DK. Functional organization of mammalian hexokinase II. Retention of catalytic and regulatory functions in both the NH2- and COOH-terminal halves. J Biol Chem, 271(4), 1849-52, 1996.

Ardehali, H., Yano, Y., Printz, R.L., Koch, S., Whitesell, R.R., May, J.M. and Granner, D.K. Functional Organization of Mammalian Hexokinase II. J. Biol. Chem., 271, 1849-1852, 1996.

Chang, P.-Y., Jensen, J., Printz, R.L., Granner, D.K., Ivy, J.L. and Moller, D.E. Overexpression of Hexokinase II in Transgenic Mice: Evidence that Increased Phosphorylation Augments Muscle Glucose Uptake. J. Biol. Chem., 271, 14834-14839, 1996.

O''Brien, RM, Granner, DK. Regulation of gene expression by insulin. Physiol Rev, 76(4), 1109-61, 1996.

O''Doherty, RM, Bracy, DP, Granner, DK, Wasserman, DH. Transcription of the rat skeletal muscle hexokinase II gene is increased by acute exercise. J Appl Physiol, 81(2), 789-93, 1996.

O'Brien, R.M., Granner, D.K. The Regulation of Gene Expression by Insulin. Physiological Reviews, 76, 1109-1161, 1996.

O'Doherty, R.M., Bracy, D.P., Granner, D.K. and Wasserman, D.H. Transcription of the Rat Skeletal Muscle Hexokinase II Gene is Increased by Acute Exercise. J. Appl. Physiol., 81, 789-793, 1996.

Osawa, H, Robey, RB, Printz, RL, Granner, DK. Identification and characterization of basal and cyclic AMP response elements in the promoter of the rat hexokinase II gene. J Biol Chem, 271(29), 17296-303, 1996.

Osawa, H, Sutherland, C, Robey, RB, Printz, RL, Granner, DK. Analysis of the signaling pathway involved in the regulation of hexokinase II gene transcription by insulin. J Biol Chem, 271(28), 16690-4, 1996.

Osawa, H., Robey, R.B., Printz, R.L. and Granner, D.K. Identification and Characterization of Basal and Cyclic AMP Response Elements in the Promoter of the Rat Hexokinase II Gene. J. Biol. Chem., 271, 17296-17303, 1996.

Osawa, H., Sutherland, C., Robey, R.B., Printz, R.L. and Granner, D.K. Analysis of the Signaling Pathway Involved in the Regulation of Hexokinase II Gene Transcription by Insulin. J. Biol. Chem., 271, 16690-16694, 1996.

Robey, RB, Osawa, H, Printz, RL, Granner, DK. Transient gene transfer into myotubes following differentiation in culture. Biotechniques, 20(1), 40-2, 1996.

Scott, D.K., Mitchell, J.A. and Granner, D.K. Identification and Characterization of a Second Retinoic Acid Response Element in the Phosphoenolpyruvate Carboxykinase Gene Promoter. J. Biol. Chem., 271, 6260-6264, 1996.

Scott, D.K., Mitchell, J.A. and Granner, D.K. The Orphan Receptor COUP-TF Binds to a Third Glucocorticoid Accessory Factor Element Within the Phosphoenolpyruvate Carboxykinase Gene Promoter. J. Biol. Chem., 271, 31909-31914, 1996.

Scott, DK, Mitchell, JA, Granner, DK. The orphan receptor COUP-TF binds to a third glucocorticoid accessory factor element within the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem, 271(50), 31909-14, 1996.

Scott, DK, Mitchell, JA, Granner, DK. Identification and charaterization of the second retinoic acid response element in the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem, 271(11), 6260-4, 1996.

Sutherland, C, O''Brien, RM, Granner, DK. New connections in the regulation of PEPCK gene expression by insulin. Philos Trans R Soc Lond B Biol Sci, 351(1336), 191-9, 1996.

Wang, J.-C., Stromstedt, P.-E., O'Brien, R.M. and Granner, D.K. Hepatic Nuclear Factor 3 is an Accessory Factor Required for the Stimulation of Phosphoenolpyruvate Carboxykinase Gene Transcription by Glucocorticoids. Mol. Endocrinol., 10, 794-800, 1996.

Wang, JC, Str??mstedt, PE, O''Brien, RM, Granner, DK. Hepatic nuclear factor 3 is an accessory factor required for the stimulation of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. Mol Endocrinol, 10(7), 794-800, 1996.

Ardehali, H, Printz, RL, Koch, S, Phillips, JA, Granner, DK. Isolation, characterization and chromosomal localization of a human pseudogene for hexokinase II. Gene, 164(2), 357-61, 1995.

Hall, R.K., Sladek, F.M. and Granner, D.K. The orphan receptors COUP-TF and HNF-4 serve as accessory factors required for induction of the phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. Proc. Nat'l. Acad. Sci., 92, 412-416, 1995.

Hall, RK, Sladek, FM, Granner, DK. The orphan receptors COUP-TF and HNF-4 serve as accessory factors required for induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids. Proc Natl Acad Sci U S A, 92(2), 412-6, 1995.

Mandarino, L.J., Printz, R.K., Cusi, K.A., Kinchington, P., O'Doherty, R.M., Osawa, H., Sewell, C., Consoli, A., Granner, D.K. and DeFronzo, R.A. Regulation of Hexokinase II and Glycogen Synthase mRNA, Protein, and Catalytic Activity in Human Skeletal Muscle In Vivo. Am. J. Physiol., , E701-E708, 1995.

O''Brien, RM, Halmi, N, Stromstedt, PE, Printz, RL, Granner, DK. Expression cloning of a zinc-finger cyclic AMP-response-element-binding protein. Biochem J, 312 ( Pt 1), 17-21, 1995.

O''Brien, RM, Noisin, EL, Suwanichkul, A, Yamasaki, T, Lucas, PC, Wang, JC, Powell, DR, Granner, DK. Hepatic nuclear factor 3- and hormone-regulated expression of the phosphoenolpyruvate carboxykinase and insulin-like growth factor-binding protein 1 genes. Mol Cell Biol, 15(3), 1747-58, 1995.

O''Brien, RM, Printz, RL, Halmi, N, Tiesinga, JJ, Granner, DK. Structural and functional analysis of the human phosphoenolpyruvate carboxykinase gene promoter. Biochim Biophys Acta, 1264(3), 284-8, 1995.

O'Brien, R.M., Noisin, E.L., Suwanickul, A., Yamasaki, T., Lucas, P.C., Wang, J.-C., Powell, D.R. and Granner, D.K. Hepatic nuclear factor-3 and hormone regulated expression of the PEPCK and IGFBP-1 genes. Mol. Cell. Biol., 15, 1747-1758, 1995.

Osawa, H, Printz, RL, Whitesell, RR, Granner, DK. Regulation of hexokinase II gene transcription and glucose phosphorylation by catecholamines, cyclic AMP, and insulin. Diabetes, 44(12), 1426-32, 1995.

Postic, C, Niswender, KD, Decaux, JF, Parsa, R, Shelton, KD, Gouhot, B, Pettepher, CC, Granner, DK, Girard, J, Magnuson, MA. Cloning and characterization of the mouse glucokinase gene locus and identification of distal liver-specific DNase I hypersensitive sites. Genomics, 29(3), 740-50, 1995.

Printz, RL, Ardehali, H, Koch, S, Granner, DK. Human hexokinase II mRNA and gene structure. Diabetes, 44(3), 290-4, 1995.

Scott, DK, Hall, RK, Granner, DK. Retinoid receptors cause distortion of the retinoic acid response element in the phosphoenolpyruvate carboxykinase gene promoter. Biochem J, 310 ( Pt 2), 483-90, 1995.

Sutherland, C, O''Brien, RM, Granner, DK. Phosphatidylinositol 3-kinase, but not p70/p85 ribosomal S6 protein kinase, is required for the regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by insulin. Dissociation of signaling pathways for insulin and phorbol ester regulation of PEPCK gene expression. J Biol Chem, 270(26), 15501-6, 1995.

Tebbey, PW, Hall, RK, Granner, DK. The role of the TATA box in the hormonal regulation of phosphoenolpyruvate carboxykinase gene expression. Biochem Biophys Res Commun, 215(3), 1006-13, 1995.

Whitesell, RR, Ward, M, McCall, AL, Granner, DK, May, JM. Coupled glucose transport and metabolism in cultured neuronal cells: determination of the rate-limiting step. J Cereb Blood Flow Metab, 15(5), 814-26, 1995.

Williams, CP, Granner, DK, Magnuson, MA, Chalkley, R. Cell specific differences in DNase I hypersensitivity between the two promoters of the rat glucokinase gene. Biochem Biophys Res Commun, 215(1), 272-9, 1995.

Mitchell, J., Noisin, E., Hall, R., O'Brien, R., Imai, E. and Granner, D. Integration of Multiple Signals Through a Complex Hormone Response Unit in the Phosphoenolpyruvate Carboxykinase Gene Promoter. Molec. Endo., , 8, 545-594, 1994.

Morita, H, Yano, Y, Niswender, KD, May, JM, Whitesell, RR, Wu, L, Printz, RL, Granner, DK, Magnuson, MA, Powers, AC. Coexpression of glucose transporters and glucokinase in Xenopus oocytes indicates that both glucose transport and phosphorylation determine glucose utilization. J Clin Invest, 94(4), 1373-82, 1994.

O''Brien, RM, Lucas, PC, Yamasaki, T, Noisin, EL, Granner, DK. Potential convergence of insulin and cAMP signal transduction systems at the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter through CCAAT/enhancer binding protein (C/EBP). J Biol Chem, 269(48), 30419-28, 1994.

O''Brien, RM, Noisin, EL, Granner, DK. Comparison of the effects of insulin and okadaic acid on phosphoenolpyruvate carboxykinase gene expression. Biochem J, 303 ( Pt 3), 737-42, 1994.

O''Doherty, RM, Bracy, DP, Osawa, H, Wasserman, DH, Granner, DK. Rat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise. Am J Physiol, 266(2 Pt 1), E171-8, 1994.

O'Doherty, R.M., Bracy, D.P., Osawa, H., Wasserman, D.H. and Granner, D.K. Rat Skeletal Muscle Hexokinase II mRNA and Activity are Increased by a Single Bout of Acute Exercise. Am. J. Physiol, , E171-E178, 1994.

Faber, S, O''Brien, RM, Imai, E, Granner, DK, Chalkley, R. Dynamic aspects of DNA/protein interactions in the transcriptional initiation complex and the hormone-responsive domains of the phosphoenolpyruvate carboxykinase promoter in vivo. J Biol Chem, 268(33), 24976-85, 1993.

Imai, E, Miner, JN, Mitchell, JA, Yamamoto, KR, Granner, DK. Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids. J Biol Chem, 268(8), 5353-6, 1993.

Imai, E., Miner, J., Mitchell, J., Yamamoto, K.Y. and Granner, D. Glucocorticoid Receptor-CREB Interaction and the Response of the PEPCK Gene to Glucocorticoids. J. Biol. Chem., 268, 5353-5356, 1993.

O''Brien, RM, Lucas, PC, Yamasaki, T, Granner, DK. The physiological importance of insulin regulated gene expression: metabolic and molecular studies. Adv Second Messenger Phosphoprotein Res, 28, 245-53, 1993.

Printz, R.L., Koch, S., Potter, L.R., O'Doherty, R.M., Tiesinga, J.J., Moritz, S. and Granner, D.K. Hexokinase II mRNA and Gene Structure, Regulation by Insulin and Evolution. J. Biol. Chem., 268, 5209-5219, 1993.

Printz, R.L., Magnuson, M.A. and Granner, D.K. Mammalian Glucokinase. Ann Rev. Nut, 13, 463-496, 1993.

Printz, RL, Koch, S, Potter, LR, O''Doherty, RM, Tiesinga, JJ, Moritz, S, Granner, DK. Hexokinase II mRNA and gene structure, regulation by insulin, and evolution. J Biol Chem, 268(7), 5209-19, 1993.

Printz, RL, Magnuson, MA, Granner, DK. Mammalian glucokinase. Annu Rev Nutr, 13, 463-96, 1993.

Granner, D.K. and O'Brien, R.M. Molecular Physiology and Genetics of NIDDM. Diabetes Care, 15, 369-395, 1992.

Granner, DK, O''Brien, RM. Molecular physiology and genetics of NIDDM. Importance of metabolic staging. Diabetes Care, 15(3), 369-95, 1992.

Hall, R., Scott, D.K., Noisin, E.L., Lucas, P. and Granner, D.K. Activation of the PEPCK Retinoic Acid Response Element is Dependent on a Retinoic Acid Receptor/Coregulator Complex. Mol. Cell Biol., 12, 5527-5535, 1992.

Hall, RK, Scott, DK, Noisin, EL, Lucas, PC, Granner, DK. Activation of the phosphoenolpyruvate carboxykinase gene retinoic acid response element is dependent on a retinoic acid receptor/coregulator complex. Mol Cell Biol, 12(12), 5527-35, 1992.

Lucas, P. and Granner, D. Hormone Response Domains in Gene Transcription. Ann. Rev. Biochem., 61, 1131-1173, 1992.

Lucas, PC, Granner, DK. Hormone response domains in gene transcription. Annu Rev Biochem, 61, 1131-73, 1992.

O''Brien, RM, Lucas, PC, Yamasaki, T, Bonovich, MT, Forest, CD, Granner, DK. Insulin and phorbol esters act through the same DNA element to inhibit phosphoenolpyruvate carboxykinase gene transcription. Biochem Soc Trans, 20(3), 686-90, 1992.

Lucas, PC, Forman, BM, Samuels, HH, Granner, DK. Specificity of a retinoic acid response element in the phosphoenolpyruvate carboxykinase gene promoter: consequences of both retinoic acid and thyroid hormone receptor binding. Mol Cell Biol, 11(12), 6343, 1991.

Lucas, PC, Forman, BM, Samuels, HH, Granner, DK. Specificity of a retinoic acid response element in the phosphoenolpyruvate carboxykinase gene promoter: consequences of both retinoic acid and thyroid hormone receptor binding. Mol Cell Biol, 11(10), 5164-70, 1991.

Lucas, PC, O''Brien, RM, Mitchell, JA, Davis, CM, Imai, E, Forman, BM, Samuels, HH, Granner, DK. A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. Proc Natl Acad Sci U S A, 88(6), 2184-8, 1991.

O''Brien, RM, Bonovich, MT, Forest, CD, Granner, DK. Signal transduction convergence: phorbol esters and insulin inhibit phosphoenolpyruvate carboxykinase gene transcription through the same 10-base-pair sequence. Proc Natl Acad Sci U S A, 88(15), 6580-4, 1991.

O''Brien, RM, Granner, DK. Regulation of gene expression by insulin. Biochem J, 278 ( Pt 3), 609-19, 1991.

Forest, CD, O''Brien, RM, Lucas, PC, Magnuson, MA, Granner, DK. Regulation of phosphoenolpyruvate carboxykinase gene expression by insulin. Use of the stable transfection approach to locate an insulin responsive sequence. Mol Endocrinol, 4(9), 1302-10, 1990.

Imai, E, Stromstedt, PE, Quinn, PG, Carlstedt-Duke, J, Gustafsson, JA, Granner, DK. Characterization of a complex glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol, 10(9), 4712-9, 1990.

Ip, YT, Poon, D, Stone, D, Granner, DK, Chalkley, R. Interaction of a liver-specific factor with an enhancer 4.8 kilobases upstream of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol, 10(7), 3770-81, 1990.

O''Brien, RM, Granner, DK. PEPCK gene as model of inhibitory effects of insulin on gene transcription. Diabetes Care, 13(3), 327-39, 1990.

O''Brien, RM, Lucas, PC, Forest, CD, Magnuson, MA, Granner, DK. Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription. Science, 249(4968), 533-7, 1990.

Quinn, PG, Granner, DK. Cyclic AMP-dependent protein kinase regulates transcription of the phosphoenolpyruvate carboxykinase gene but not binding of nuclear factors to the cyclic AMP regulatory element. Mol Cell Biol, 10(7), 3357-64, 1990.

Andreone, TL, Printz, RL, Pilkis, SJ, Magnuson, MA, Granner, DK. The amino acid sequence of rat liver glucokinase deduced from cloned cDNA. J Biol Chem, 264(1), 363-9, 1989.

Chrapkiewicz, NB, Davis, CM, Chu, DT, Caldwell, CM, Granner, DK. Rat gene 33: analysis of its structure, messenger RNA and basal promoter activity. Nucleic Acids Res, 17(16), 6651-67, 1989.

Ip, YT, Granner, DK, Chalkley, R. Hormonal regulation of phosphoenolpyruvate carboxykinase gene expression is mediated through modulation of an already disrupted chromatin structure. Mol Cell Biol, 9(3), 1289-97, 1989.

Magnuson, MA, Andreone, TL, Printz, RL, Koch, S, Granner, DK. Rat glucokinase gene: structure and regulation by insulin. Proc Natl Acad Sci U S A, 86(13), 4838-42, 1989.

Petersen, DD, Koch, SR, Granner, DK. 3'' noncoding region of phosphoenolpyruvate carboxykinase mRNA contains a glucocorticoid-responsive mRNA-stabilizing element. Proc Natl Acad Sci U S A, 86(20), 7800-4, 1989.

Chu, DT, Davis, CM, Chrapkiewicz, NB, Granner, DK. Reciprocal regulation of gene transcription by insulin. Inhibition of the phosphoenolpyruvate carboxykinase gene and stimulation of gene 33 in a single cell type. J Biol Chem, 263(26), 13007-11, 1988.

Colosia, AD, Marker, AJ, Lange, AJ, el-Maghrabi, MR, Granner, DK, Tauler, A, Pilkis, J, Pilkis, SJ. Induction of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA by refeeding and insulin. J Biol Chem, 263(35), 18669-77, 1988.

Corbin, JD, Cobb, CE, Beebe, SJ, Granner, DK, Koch, SR, Gettys, TW, Blackmore, PF, Francis, SH, Wells, JN. Mechanism and function of cAMP- and cGMP-dependent protein kinases. Adv Second Messenger Phosphoprotein Res, 21, 75-86, 1988.

Petersen, DD, Magnuson, MA, Granner, DK. Location and characterization of two widely separated glucocorticoid response elements in the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol, 8(1), 96-104, 1988.

Quinn, PG, Wong, TW, Magnuson, MA, Shabb, JB, Granner, DK. Identification of basal and cyclic AMP regulatory elements in the promoter of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol, 8(8), 3467-75, 1988.

Sasaki, K, Granner, DK. Regulation of phosphoenolpyruvate carboxykinase gene transcription by insulin and cAMP: reciprocal actions on initiation and elongation. Proc Natl Acad Sci U S A, 85(9), 2954-8, 1988.

Shabb, JB, Granner, DK. Separation of topoisomerase I activity from the regulatory subunit of type II cyclic adenosine monophosphate-dependent protein kinase. Mol Endocrinol, 2(4), 324-31, 1988.

Beebe, SJ, Koch, SR, Chu, DT, Corbin, JD, Granner, DK. Regulation of phosphoenolpyruvate carboxykinase gene transcription in H4IIE hepatoma cells: evidence for a primary role of the catalytic subunit of 3'',5''-cyclic adenosine monophosphate-dependent protein kinase. Mol Endocrinol, 1(9), 639-47, 1987.

Chu, DT, Stumpo, DJ, Blackshear, PJ, Granner, DK. The inhibition of phosphoenolpyruvate carboxykinase (guanosine triphosphate) gene expression by insulin is not mediated by protein kinase C. Mol Endocrinol, 1(1), 53-9, 1987.

Granner, DK. The molecular biology of insulin action on protein synthesis. Kidney Int Suppl, 23, S82-96, 1987.

Magnuson, MA, Quinn, PG, Granner, DK. Multihormonal regulation of phosphoenolpyruvate carboxykinase-chloramphenicol acetyltransferase fusion genes. Insulin''s effects oppose those of cAMP and dexamethasone. J Biol Chem, 262(31), 14917-20, 1987.


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