Vanderbilt University School of Medicine

McGuinness, Owen Patrick , Ph.D.
Professor of Molecular Physiology and Biophysics

Lab Url: http://www.mc.vanderbilt.edu/root/vumc.php?site=mmpc&doc=3683

Phone Number: 615-343-4473

Email Address:Owen.McGuinness@vanderbilt.edu

McGuinness, Owen's picture

Office Address   Mailing Address

831c Light hall

702 Light hall 0615


Research Keywords
Infection, Tumor Necrosis Factor, Nitric Oxide, Glucose Metabolism, NFkappB,Diabetes,Endocrinology,Immunology,Knockout,Mouse,Physiology

Research Specialty
Regulation Of Metabolic Response to Inflammation: Interaction With Nutrition

Research Description
Our studies focus on the regulation of hepatic and muscle glucose disposal during infection and inflammation. We examine its interaction with obesity and nutritional support. Our approach is to assess metabolism using a combination of tracer and arterio-venous difference techniques in conscious chronically catheterized conscious dogs and mice. We use a combination of pharmacological and surgical approaches to dissect the role that individual hormones and other mediators might play in the response. In addition we take advantage of genetically modified mouse models to determine the role inflammatory mediators play in controlling the metabolic response to infection and obesity. In our canine model, we observed that the liver is a major site of glucose disposal in a normal animal receiving nutritional support. We have also observed that the presence of an infection impairs hepatic glucose uptake in animals receiving nutritional support. Our studies address the mechanism for the impairment in liver glucose uptake and the role that elevations in glucagon, substrate supply, route of nutrient delivery and nitric oxide might play in contributing to or correcting the alteration. In our mouse model, we are developing strategies to examine the interaction of inflammation and obesity in a high fat fed mouse model. We are examining the role that NFkappaB plays in contributing to observed impairment in insulin action. In addition we are assessing the mechanism whereby interleukin-6 (a cytokine that is increased in metabolic disease) augments glucagon secretion.
Possible rotation projects: 1. Glucagon plays an important role in determining the ability of the liver to adapt to nutritional support. The project will focus on the interaction of glucagon with other factors that may play an important role in the adaptive response of the liver. 2. What is unclear is the molecular mechanism for the adaptation of the liver to total parenteral nutrition. The goal of this project is to determine which glucoregulatory enzymes are responsible for the adaptation of the liver to total parenteral nutrition. 3. Recent work suggests that accompanying inflammatory events may contribute to the insulin resistance seen in high fat fed states. Studies are ongoing to determine how obesity and inflammation interact to limit insulin action in muscle and liver. 4. Defects in hepatic lipid handling in insulin resistant states can lead to the accumulation of fat in the liver studies will develop methods to assess the metabolic source of the lipid that accumulates in the liver using state of the art stable isotopic methodology.

Publications
Kocalis, HE, Turney, MK, Printz, RL, Laryea, GN, Muglia, LJ, Davies, SS, Stanwood, GD, McGuinness, OP, Niswender, KD. Neuron-specific deletion of peroxisome proliferator-activated receptor delta (PPAR??) in mice leads to increased susceptibility to diet-induced obesity. PLoS One, 7(8), e42981, 2012.

Mulligan, KX, Morris, RT, Otero, YF, Wasserman, DH, McGuinness, OP. Disassociation of muscle insulin signaling and insulin-stimulated glucose uptake during endotoxemia. PLoS One, 7(1), e30160, 2012.

Pound, LD, Sarkar, SA, Ustione, A, Dadi, PK, Shadoan, MK, Lee, CE, Walters, JA, Shiota, M, McGuinness, OP, Jacobson, DA, Piston, DW, Hutton, JC, Powell, DR, O''Brien, RM. The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background. PLoS One, 7(7), e40972, 2012.

Ayala, JE, Bracy, DP, Malabanan, C, James, FD, Ansari, T, Fueger, PT, McGuinness, OP, Wasserman, DH. Hyperinsulinemic-euglycemic clamps in conscious, unrestrained mice. J Vis Exp, (57), , 2011.

Tweedell, A, Mulligan, KX, Martel, JE, Chueh, FY, Santomango, T, McGuinness, OP. Metabolic response to endotoxin in vivo in the conscious mouse: role of interleukin-6. Metabolism, 60(1), 92-8, 2011.

Yin, DP, Gao, Q, Ma, LL, Yan, W, Williams, PE, McGuinness, OP, Wasserman, DH, Abumrad, NN. Assessment of different bariatric surgeries in the treatment of obesity and insulin resistance in mice. Ann Surg, 254(1), 73-82, 2011.

Ayala, JE, Samuel, VT, Morton, GJ, Obici, S, Croniger, CM, Shulman, GI, Wasserman, DH, McGuinness, OP, , . Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Dis Model Mech, 3(9-10), 525-34, 2010.

Johnson, PM, Chen, SS, Santomango, TS, Williams, PE, Lacy, DB, McGuinness, OP. Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization. Metabolism, , , 2010.

Shi, S, Hida, A, McGuinness, OP, Wasserman, DH, Yamazaki, S, Johnson, CH. Circadian clock gene Bmal1 is not essential; functional replacement with its paralog, Bmal2. Curr Biol, 20(4), 316-21, 2010.

Chen, SS, Santomango, TS, Williams, PE, Lacy, DB, McGuinness, OP. Glucagon mediated impairments in hepatic and peripheral tissue nutrient disposal are not amplified by increased lipid availability. Am J Physiol Endocrinol Metab, , , 2009. PMCID:2681308

Lee-Young, RS, Griffee, SR, Lynes, SE, Bracy, DP, Ayala, JE, McGuinness, OP, Wasserman, DH. Skeletal muscle AMP-activated protein kinase is essential for the metabolic response to exercise in vivo. J Biol Chem, 284(36), 23925-34, 2009. PMCID:2781986

McGuinness, OP, Ayala, JE, Laughlin, MR, Wasserman, DH. NIH Experiment in Centralized Mouse Phenotyping: The Vanderbilt Experience and Recommendations for Evaluating Glucose Homeostasis in the Mouse. Am J Physiol Endocrinol Metab, , , 2009.

Pound, LD, Sarkar, SA, Benninger, RK, Wang, Y, Suwanichkul, A, Shadoan, MK, Printz, RL, Oeser, JK, Lee, CE, Piston, DW, McGuinness, OP, Hutton, JC, Powell, DR, O''Brien, RM. Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion. Biochem J, 421(3), 371-6, 2009. PMCID:2929527

Wasserman, DH, Ayala, JE, McGuinness, OP. Lost in translation. Diabetes, 58(9), 1947-50, 2009. PMCID:2731517

Chen, SS, Zhang, Y, Santomango, TS, Williams, PE, Lacy, DB, McGuinness, OP. Glucagon chronically impairs hepatic and muscle glucose disposal. Am J Physiol Endocrinol Metab, 292(3), E928-35, 2007.

De Taeye, BM, Novitskaya, T, McGuinness, OP, Gleaves, L, Medda, M, Covington, JW, Vaughan, DE. Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity. Am J Physiol Endocrinol Metab, 293(3), E713-25, 2007.

Rao, R, Hao, CM, Redha, R, Wasserman, DH, McGuinness, OP, Breyer, MD. Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL/6J mice. Diabetologia, 50(2), 452-60, 2007. PMCID:2681308

Wang, Y, Martin, CC, Oeser, JK, Sarkar, S, McGuinness, OP, Hutton, JC, O''Brien, RM. Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype. Diabetologia, 50(4), 774-8, 2007. PMCID:2681308

Ayala, JE, Bracy, DP, McGuinness, OP, Wasserman, DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes, 55(2), 390-7, 2006.

Chueh, FY, Malabanan, C, McGuinness, OP. Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice. Am J Physiol Endocrinol Metab, 291(6), E1206-11, 2006.

Wang, Y, Oeser, JK, Yang, C, Sarkar, S, Hackl, SI, Hasty, AH, McGuinness, OP, Paradee, W, Hutton, JC, Powell, DR, O''Brien, RM. Deletion of the gene encoding the ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein (UGRP)/glucose-6-phosphatase catalytic subunit-beta results in lowered plasma cholesterol and elevated glucagon. J Biol Chem, 281(52), 39982-9, 2006. PMCID:2681308

Chen, SS, Torres-Sanchez, CJ, Hosein, N, Zhang, Y, Lacy, DB, Chang, C, McGuinness, OP. Route-dependent effect of nutritional support on liver glucose uptake. Am J Physiol Regul Integr Comp Physiol, 289(5), R1319-27, 2005.

Chen, SS, Torres-Sanchez, CJ, Hosein, N, Zhang, Y, Lacy, DB, McGuinness, OP. Time course of the hepatic adaptation to TPN: interaction with glycogen depletion. Am J Physiol Endocrinol Metab, 288(1), E163-70, 2005.

Grubert, JM, Lautz, M, Lacy, DB, Moore, MC, Farmer, B, Penaloza, A, Cherrington, AD, McGuinness, OP. Impact of continuous and pulsatile insulin delivery on net hepatic glucose uptake. Am J Physiol Endocrinol Metab, 289(2), E232-40, 2005.

McGuinness, OP. Defective glucose homeostasis during infection. Annu Rev Nutr, 25, 9-35, 2005.

Chen, Sheng-Song, Donmoyer, Christine M, Pearson, David A, Poole, Adrian, Zhang, Yiqun, Lacy, D Brooks, McGuinness, Owen P. Impact of infection on glucose-dependent liver glucose uptake during TPN: interaction with insulin. Am J Physiol Endocrinol Metab, 286(2), E286-95, 2004.

Ma, Li-Jun, Mao, Su-Li, Taylor, Kevin L, Kanjanabuch, Talerngsak, Guan, YouFei, Zhang, YaHua, Brown, Nancy J, Swift, Larry L, McGuinness, Owen P, Wasserman, David H, Vaughan, Douglas E, Fogo, Agnes B. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes, 53(2), 336-46, 2004.

McGuinness, OP. Defective Glucose Homeostasis During Infection. Annu Rev Nutr, , , 2004.

Rocheleau, JV, Walker, GM, Head, WS, McGuinness, OP, Piston, DW. Microfluidic glucose stimulation reveals limited coordination of intracellular Ca2+ activity oscillations in pancreatic islets. Proc Natl Acad Sci U S A, 101(35), 12899-903, 2004. PMCID:516492

Donmoyer, Christine M, Chen, Sheng-Song, Lacy, D Brooks, Pearson, David A, Poole, Adrian, Zhang, Yiqun, McGuinness, Owen P. Infection impairs insulin-dependent hepatic glucose uptake during total parenteral nutrition. Am J Physiol Endocrinol Metab, 284(3), E574-82, 2003.

McGuinness, Owen P, Cherrington, Alan D. Effects of fructose on hepatic glucose metabolism. Curr Opin Clin Nutr Metab Care, 6(4), 441-8, 2003.

Chen, Sheng-Song, Donmoyer, Christine M, Ejiofor, Joseph, McCay, Juli, Archuletta, Richard, Lacy, D Brooks, McGuinness, Owen P. Impact of intraportal N(omega)-nitro-L-arginine infusion on hepatic glucose metabolism in total parenteral nutrition-adapted dogs: interaction with infection. Metabolism, 51(3), 274-83, 2002.

Cherrington, Alan D, Sindelar, Dana, Edgerton, Dale, Steiner, Kurt, McGuinness, Owen P. Physiological consequences of phasic insulin release in the normal animal. Diabetes, 51 Suppl 1, S103-8, 2002.

Donmoyer, Christine M, Lacy, D Brooks, Zhang, Yiqun, Chen, Sheng-Song, McGuinness, Owen P. Impact of chronic fructose infusion on hepatic metabolism during TPN administration. Am J Physiol Endocrinol Metab, 283(6), E1151-8, 2002.

Mandarino,L.J. Bonadonna,R. McGuinness,O.P. and Wasserman,D.H. Regulation of muscle glucose uptake in vivo Handbook of Physiology Section VII, Vol. 2, pp 803-845, 2001.

Donmoyer, C M, Ejiofor, J, Lacy, D B, Chen, S S, McGuinness, O P. Fructose augments infection-impaired net hepatic glucose uptake during TPN administration. Am J Physiol Endocrinol Metab, 280(5), E703-11, 2001.

38. Song-Chen, S., Donmoyer, C.M. , Zhang, Y., Hande, S.A., Lacy D.B. and McGuinness,O.P. Impact of Enteral and Parenteral Nutrition on Hepatic and Muscle Glucose Metabolism. JPEN 24:255-260,2000

39. C.M. Donmoyer, Song-Chen, S., Hande, S.A., Lacy D.B., J.E. Ejiofor and McGuinness,O.P. Hyperinsulinemia compensates for infection-induced impairment in net hepatic glucose uptake during TPN administration. Amer. J. Physiol 279:E235-E243,2000

McGuinness, O.P., J. E. Ejiofor, Lacy, D.B. and Schrom N. Hepatic glucose metabolism during intraduodenal glucose infusion: Impact of infection Amer. J. Physiol (279:E108-E115, 2000.

Song-Chen, S., Donmoyer, C.M. , Zhang, Y., Hande, S.A., Lacy D.B. and McGuinness,O.P. Impact of Enteral and Parenteral Nutrition on Hepatic and Muscle Glucose Metabolism. JPEN 24:255-250, 2000.

Chen, S S, Donmoyer, C, Zhang, Y, Hande, S A, Lacy, D B, McGuinness, O P. Impact of enteral and parenteral nutrition on hepatic and muscle glucose metabolism. JPEN J Parenter Enteral Nutr, 24(5), 255-60, 2000.

Donmoyer, C M, Chen, S S, Hande, S A, Lacy, D B, Ejiofor, J, McGuinness, O P. Hyperinsulinemia compensates for infection-induced impairment in net hepatic glucose uptake during TPN. Am J Physiol Endocrinol Metab, 279(2), E235-43, 2000.

McGuinness, O P, Ejiofor, J, Lacy, D B, Schrom, N. Hepatic glucose metabolism during intraduodenal glucose infusion: impact of infection. Am J Physiol Endocrinol Metab, 279(1), E108-15, 2000.

McGuinness, O.P. Snowden, R.T., Moran C, Neal,D.W., Fujiwara,T. and A.D. Cherrington. Impact of acute epinephrine removal on hepatic glucose metabolism during stress hormone infusion Metabolism 48: 910-914,1999.

McGuinness, O P, Snowden, R T, Moran, C, Neal, D W, Fujiwara, T, Cherrington, A D. Impact of acute epinephrine removal on hepatic glucose metabolism during stress hormone infusion. Metabolism, 48(7), 910-4, 1999.

Lang, C.H., R.A. Frost, J. Ejiofor, D.B. Lacy, and O.P. McGuinness. Hepatic production and intestinal uptake of IGF-1: response to infection. Am.J.Physiol 275:G1291-G1298, 1998.

McGuinness, O.P., Ejiofor,J., Audolay L.P. and Schrom N. Regulation of glucose production by NEFA and gluconeogenic precursors during chronic glucagon infusion Amer. J.Physiol.275:E432-E439,1998.

McGuinness,O.P., Donmoyer, C., Ejiofor, J.E., McElligott, S. and Lacy, D.B. Hepatic and muscle glucose metabolism during total parenteral nutrition: impact of infection Amer. J. Physiol. 275:E763-E769,1998.

Meinz H. Lacy, D.B. and Ejiofor J., and McGuinness O.P. Alterations In Hepatic Gluconeogenic Amino Acid Uptake And Gluconeogenesis In The Endotoxin Treated Conscious Dog. Shock 9:296-303,1998.

McGuinness, O P, Donmoyer, C, Ejiofor, J, McElligott, S, Lacy, D B. Hepatic and muscle glucose metabolism during total parenteral nutrition: impact of infection. Am J Physiol, 275(5 Pt 1), E763-9, 1998.

McGuinness, O P, Ejiofor, J, Audoly, L P, Schrom, N. Regulation of glucose production by NEFA and gluconeogenic precursors during chronic glucagon infusion. Am J Physiol, 275(3 Pt 1), E432-9, 1998.

Meinz, H, Lacy, D B, Ejiofor, J, McGuinness, O P. Alterations in hepatic gluconeogenic amino acid uptake and gluconeogenesis in the endotoxin treated conscious dog. Shock, 9(4), 296-303, 1998.

McGuinness, O.P. and Mari, A. Assessment of insulin action on glucose uptake and production during a euglycemic hyperinsulinemic clamp in dog: A new kinetic analysis. Metabolism 46:1116-1127, 1997.

McGuinness, O.P., Shau,V.,Benson,E.Greene,J.E. Neal D.W.,and A.D. Cherrington. Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion. Am. J. Physiol .273:E6740681, 1997.

McGuinness, O P, Mari, A. Assessment of insulin action on glucose uptake and production during a euglycemic-hyperinsulinemic clamp in dog: a new kinetic analysis. Metabolism, 46(10), 1116-27, 1997.

McGuinness, O P, Shau, V, Benson, E M, Lewis, M, Snowden, R T, Greene, J E, Neal, D W, Cherrington, A D. Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog. Am J Physiol, 273(4 Pt 1), E674-81, 1997.

Fujiwara, T., Neal, D.N., Cherrington, A.D., and McGuinness, O.P. Role of cortisol in the metabolic response to stress hormone infusion. Metabolism 45:571-578,1996.

McGuinness, O.P., Lacy, D. B. and Eliasson, K. Hyperglucagonemia and hepatic glucose metabolism during infection in the conscious dog. Am. J. Physiol. 270:E580-E588,1996

McGuinness, O.P., Lacy, D.B., and Eliasson, K.E. (1996) Hyperglucagonemia and hepatic glucose metabolism during infection in the conscious dog. Am. J. Physiol. 270: E580-E586.

Fujiwara, T, Cherrington, A D, Neal, D N, McGuinness, O P. Role of cortisol in the metabolic response to stress hormone infusion in the conscious dog. Metabolism, 45(5), 571-8, 1996.

McGuinness, O P, Lacy, D B, Ejiofor, J, Bagby, G G. Hepatic release of tumor necrosis factor in the endotoxin-treated conscious dog. Shock, 5(5), 344-8, 1996.

McGuinness, O P, Lacy, D B, Eliasson, K. Hyperglucagonemia and hepatic glucose metabolism during infection in the conscious dog. Am J Physiol, 270(4 Pt 1), E580-8, 1996.

McGuinness, O.P, Jacobs, J., Moran, C. and Lacy, D.B. Impact of infection on hepatic disposal of peripheral glucose infusion in the conscious dog. Am. J. Physiol. 269:E199-E207, 1995.

McGuinness, O.P., Jacobs, J., Moran, C., and Lacy, D.B. (1995) Impact of infection on hepatic disposal of a peripheral glucose infusion in the conscious dog. Am. J. Physiol. 269:E199-E207.

McGuinness, O.P., Lacy, D. B. and Anderson, J. The effect of acute glucagon removal on the metabolic response to infectionin the conscious dog. Am. J. Physiol. 268:E92-E99, 1995.

McGuinness, O P, Jacobs, J, Moran, C, Lacy, B. Impact of infection on hepatic disposal of a peripheral glucose infusion in the conscious dog. Am J Physiol, 269(2 Pt 1), E199-207, 1995.

McGuinness, O P, Lacy, D B, Anderson, J. Effect of acute glucagon removal on metabolic response to infection in conscious dog. Am J Physiol, 268(1 Pt 1), E92-9, 1995.

Cherrington, A.D., Wasserman, D.H., and McGuinness, O.P. Renal contribution to glucose production after a brief fast: fact or fancy. J. Clin. Invest. 93:2303, 1994.

McGuinness, O.P. Assessment of Insulin Action In Vivo: Methodological Considerations. Sem. Reprod. Endocrin. 12(2):143-148, 1994.

McGuinness, O.P. Regulation of glucose metabolism during infection. In: The Role of the Liver in Maintaining Glucose Homeostasis. Pagliassotti, M., Davis, S., and Cherrington, A.D. (Eds.). R.G. Landes Company, Austin, pp 139-143, 1994.

McGuinness, O.P. The impact of infection on gluconeogenesis in the conscious dog. Shock 2:336-343, 1994.

McGuinness, O.P., Murrell, S.E., Burgin, K.E., Bracy, D.B. and Cherrington, A.D. Impact of acute glucagon removal on the metabolic response to stress hormone infusion in conscious dogs. Metabolism 43:1310-1317, 1994.

McGuinness, O P. The impact of infection on gluconeogenesis in the conscious dog. Shock, 2(5), 336-43, 1994.

McGuinness, O P, Burgin, K, Moran, C, Bracy, D, Cherrington, A D. Role of glucagon in the metabolic response to stress hormone infusion in the conscious dog. Am J Physiol, 266(3 Pt 1), E438-47, 1994.

McGuinness, O P, Murrell, S, Moran, C, Bracy, D, Cherrington, A D. The effect of acute glucagon removal on the metabolic response to stress hormone infusion in the conscious dog. Metabolism, 43(10), 1310-7, 1994.

Goldstein, R.E., Wasserman, D.H., McGuinness, O.P., Lacy, D.B., Cherrington, A.D., and Abumrad, N. The effects of a chronic elevation in plasma cortisol on carbohydrate metabolism. Am. J. Physiol. 264: E119-E127, 1993.

McGuinness, O.P., Burgin, K., Moran, C., Bracy, D. and Cherrington, A.D. Role of glucagon in the metabolic response to stress hormone infusion in the conscious dog. Am. J. Physiol. 266 :E438-E447, 1994.

McGuinness, O.P., Murrell, S.E., Bracy, D.B. and Cherrington, A.D. Impact of chronic stress hormone infusion upon hepatic carbohydrate metabolism. Am. J. Physiol. 265: E314-E322, 1993.

Goldstein, R E, Wasserman, D H, McGuinness, O P, Lacy, D B, Cherrington, A D, Abumrad, N N. Effects of chronic elevation in plasma cortisol on hepatic carbohydrate metabolism. Am J Physiol, 264(1 Pt 1), E119-27, 1993.

McGuinness, O P, Fugiwara, T, Murrell, S, Bracy, D, Neal, D, O'Connor, D, Cherrington, A D. Impact of chronic stress hormone infusion on hepatic carbohydrate metabolism in the conscious dog. Am J Physiol, 265(2 Pt 1), E314-22, 1993.

Cherrington, A.D., Pagliassotti, M.J., Myers, S.R., Adkins-Marshall, B.and McGuinness, O.P. Factors which regulate net hepatic glucose uptake in vivo. In: Journal of Parenteral and Enteral Nutrition, Ed. N. Abumrad, 15:71S-73S, 1991.

Myers, S.R., McGuinness, O.P., Neal, D. and Cherrington, A.D. Intraportal glucose delivery enhances the effects of hepatic glucose load on net hepatic glucose uptake in vivo. J. Clin. Invest. 88:158-167, 1991.

Cherrington, A D, Pagliassotti, M J, Myers, S R, Adkins-Marshall, B, McGuinness, O P. Factors which regulate net hepatic glucose uptake in vivo. JPEN J Parenter Enteral Nutr, 15(3), 71S-73S, 1991.

Myers, S R, McGuinness, O P, Neal, D W, Cherrington, A D. Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration. J Clin Invest, 87(3), 930-9, 1991. PMCID:329884

McGuinness, O.P. and Cherrington, A.D. Effect of glyburide upon hepatic glucose metabolism. Am. J. Medicine 89:26S-37S, 1990.


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
12/19/2012



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