Owen Patrick McGuinness, Ph.D.

Professor

owen.mcguinness@vanderbilt.edu

Visit Lab Site


Faculty Appointments
Professor of Molecular Physiology and Biophysics
Education
Ph.D., Physiology, Louisiana State University, Baton Rouge, LouisianaB.S., Biology, State University of New York, Stony Brook, New York
Office Address
702 Light hall
TN 0615
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.
Research Keywords
Regulation Of Metabolic Response to Inflammation: Interaction With Nutrition
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 (PPARd) in mice leads to increased susceptibility to diet-induced obesity. PLoS ONE [print-electronic]. 2012; 7(8): e42981. PMID: 22916190, PMCID: PMC3423438, PII: PONE-D-12-05087, DOI: 10.1371/journal.pone.0042981, ISSN: 1932-6203.

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 [print-electronic]. 2012; 7(7): e40972. PMID: 22829903, PMCID: PMC3400647, PII: PONE-D-11-24034, DOI: 10.1371/journal.pone.0040972, ISSN: 1932-6203.

Mulligan KX, Morris RT, Otero YF, Wasserman DH, McGuinness OP. Disassociation of muscle insulin signaling and insulin-stimulated glucose uptake during endotoxemia. PLoS ONE [print-electronic]. 2012; 7(1): e30160. PMID: 22276152, PMCID: PMC3262801, PII: PONE-D-11-12927, DOI: 10.1371/journal.pone.0030160, ISSN: 1932-6203.

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. 2011 Jul; 254(1): 73-82. PMID: 21522012, PMCID: PMC3115424, DOI: 10.1097/SLA.0b013e3182197035, ISSN: 1528-1140.

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. Metab. Clin. Exp [print-electronic]. 2011 Jun; 60(6): 867-73. PMID: 20940071, PMCID: PMC3736817, PII: S0026-0495(10)00288-X, DOI: 10.1016/j.metabol.2010.08.006, ISSN: 1532-8600.

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. Metab. Clin. Exp [print-electronic]. 2011 Jan; 60(1): 92-8. PMID: 20102773, PMCID: PMC2889039, PII: S0026-0495(09)00534-4, DOI: 10.1016/j.metabol.2009.12.022, ISSN: 1532-8600.

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. 2011; (57): PMID: 22126863, PMCID: PMC3308587, PII: 3188, DOI: 10.3791/3188, ISSN: 1940-087X.

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 [print-electronic]. 2010 Sep; 3(9-10): 525-34. PMID: 20713647, PMCID: PMC2938392, PII: dmm.006239, DOI: 10.1242/dmm.006239, ISSN: 1754-8411.

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 [print-electronic]. 2010 Feb 2/23/2010; 20(4): 316-21. PMID: 20153195, PMCID: PMC2907674, PII: S0960-9822(09)02158-7, DOI: 10.1016/j.cub.2009.12.034, ISSN: 1879-0445.

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 [print-electronic]. 2009 Oct; 297(4): E849-55. PMID: 19638507, PMCID: PMC2763792, PII: 90996.2008, DOI: 10.1152/ajpendo.90996.2008, ISSN: 1522-1555.

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 [print-electronic]. 2009 Sep 9/4/2009; 284(36): 23925-34. PMID: 19525228, PMCID: PMC2781986, PII: M109.021048, DOI: 10.1074/jbc.M109.021048, ISSN: 0021-9258.

Wasserman DH, Ayala JE, McGuinness OP. Lost in translation. Diabetes. 2009 Sep; 58(9): 1947-50. PMID: 19720822, PMCID: PMC2731517, PII: 58/9/1947, DOI: 10.2337/db09-0537, ISSN: 1939-327X.

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. 2009 Aug 8/1/2009; 421(3): 371-6. PMID: 19450229, PMCID: PMC2929527, PII: BJ20090530, DOI: 10.1042/BJ20090530, ISSN: 1470-8728.

Chen SS, Santomango TS, Williams PE, Lacy DB, McGuinness OP. Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2009 May; 296(5): E1172-8. PMID: 19208853, PMCID: PMC2681308, PII: 90821.2008, DOI: 10.1152/ajpendo.90821.2008, ISSN: 0193-1849.

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 [print-electronic]. 2007 Sep; 293(3): E713-25. PMID: 17578885, PII: 00194.2007, DOI: 10.1152/ajpendo.00194.2007, ISSN: 0193-1849.

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 [print-electronic]. 2007 Apr; 50(4): 774-8. PMID: 17265032, DOI: 10.1007/s00125-006-0564-1, ISSN: 0012-186X.

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 [print-electronic]. 2007 Mar; 292(3): E928-35. PMID: 17132827, PII: 00063.2006, DOI: 10.1152/ajpendo.00063.2006, ISSN: 0193-1849.

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 [print-electronic]. 2007 Feb; 50(2): 452-60. PMID: 17151860, DOI: 10.1007/s00125-006-0552-5, ISSN: 0012-186X.

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 [print-electronic]. 2006 Dec 12/29/2006; 281(52): 39982-9. PMID: 17023421, PII: M605858200, DOI: 10.1074/jbc.M605858200, ISSN: 0021-9258.

Chueh FY, Malabanan C, McGuinness OP. Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2006 Dec; 291(6): E1206-11. PMID: 16822956, PII: 00608.2005, DOI: 10.1152/ajpendo.00608.2005, ISSN: 0193-1849.

Ayala JE, Bracy DP, McGuinness OP, Wasserman DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes. 2006 Feb; 55(2): 390-7. PMID: 16443772, PII: 55/2/390, ISSN: 0012-1797.

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 [print-electronic]. 2005 Nov; 289(5): R1319-27. PMID: 15994371, PII: 00175.2005, DOI: 10.1152/ajpregu.00175.2005, ISSN: 0363-6119.

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 [print-electronic]. 2005 Aug; 289(2): E232-40. PMID: 15755768, PII: 00567.2004, DOI: 10.1152/ajpendo.00567.2004, ISSN: 0193-1849.

McGuinness OP. Defective glucose homeostasis during infection. Annu. Rev. Nutr. 2005; 25: 9-35. PMID: 16011457, DOI: 10.1146/annurev.nutr.24.012003.132159, ISSN: 0199-9885.

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 [print-electronic]. 2005 Jan; 288(1): E163-70. PMID: 15339746, PII: 00192.2004, DOI: 10.1152/ajpendo.00192.2004, ISSN: 0193-1849.

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 [print-electronic]. 2004 Aug 8/31/2004; 101(35): 12899-903. PMID: 15317941, PMCID: PMC516492, PII: 0405149101, DOI: 10.1073/pnas.0405149101, ISSN: 0027-8424.

Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, Brown NJ, Swift LL, McGuinness OP, Wasserman DH, Vaughan DE, Fogo AB. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes. 2004 Feb; 53(2): 336-46. PMID: 14747283, ISSN: 0012-1797.

Chen SS, Donmoyer CM, Pearson DA, Poole A, Zhang Y, Lacy DB, McGuinness OP. Impact of infection on glucose-dependent liver glucose uptake during TPN: interaction with insulin. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2004 Feb; 286(2): E286-95. PMID: 14532169, PII: 00286.2003, DOI: 10.1152/ajpendo.00286.2003, ISSN: 0193-1849.

McGuinness OP, Cherrington AD. Effects of fructose on hepatic glucose metabolism. Curr Opin Clin Nutr Metab Care. 2003 Jul; 6(4): 441-8. PMID: 12806219, DOI: 10.1097/01.mco.0000078990.96795.cd, ISSN: 1363-1950.

Donmoyer CM, Chen SS, Lacy DB, Pearson DA, Poole A, Zhang Y, McGuinness OP. Infection impairs insulin-dependent hepatic glucose uptake during total parenteral nutrition. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2003 Mar; 284(3): E574-82. PMID: 12441309, PII: 00035.2002, DOI: 10.1152/ajpendo.00035.2002, ISSN: 0193-1849.

Donmoyer CM, Lacy DB, Zhang Y, Chen SS, McGuinness OP. Impact of chronic fructose infusion on hepatic metabolism during TPN administration. Am. J. Physiol. Endocrinol. Metab. 2002 Dec; 283(6): E1151-8. PMID: 12424103, PII: 283/6/E1151, DOI: 10.1152/ajpendo.00223.2001, ISSN: 0193-1849.

Chen SS, Donmoyer CM, Ejiofor J, McCay J, Archuletta R, Lacy DB, McGuinness OP. Impact of intraportal N(omega)-nitro-L-arginine infusion on hepatic glucose metabolism in total parenteral nutrition-adapted dogs: interaction with infection. Metab. Clin. Exp. 2002 Mar; 51(3): 274-83. PMID: 11887160, PII: S0026049502709918, ISSN: 0026-0495.

Cherrington AD, Sindelar D, Edgerton D, Steiner K, McGuinness OP. Physiological consequences of phasic insulin release in the normal animal. Diabetes. 2002 Feb; 51 Suppl 1: S103-8. PMID: 11815467, ISSN: 0012-1797.

Donmoyer CM, Ejiofor J, Lacy DB, Chen SS, McGuinness OP. Fructose augments infection-impaired net hepatic glucose uptake during TPN administration. Am. J. Physiol. Endocrinol. Metab. 2001 May; 280(5): E703-11. PMID: 11287352, ISSN: 0193-1849.

Chen SS, Donmoyer C, Zhang Y, Hande SA, Lacy DB, McGuinness OP. Impact of enteral and parenteral nutrition on hepatic and muscle glucose metabolism. JPEN J Parenter Enteral Nutr. 2000 Sep; 24(5): 255-60. PMID: 11011779, ISSN: 0148-6071.

Donmoyer CM, Chen SS, Hande SA, Lacy DB, Ejiofor J, McGuinness OP. Hyperinsulinemia compensates for infection-induced impairment in net hepatic glucose uptake during TPN. Am. J. Physiol. Endocrinol. Metab. 2000 Aug; 279(2): E235-43. PMID: 10913021, ISSN: 0193-1849.

McGuinness OP, Ejiofor J, Lacy DB, Schrom N. Hepatic glucose metabolism during intraduodenal glucose infusion: impact of infection. Am. J. Physiol. Endocrinol. Metab. 2000 Jul; 279(1): E108-15. PMID: 10893329, ISSN: 0193-1849.

McGuinness OP, Snowden RT, Moran C, Neal DW, Fujiwara T, Cherrington AD. Impact of acute epinephrine removal on hepatic glucose metabolism during stress hormone infusion. Metab. Clin. Exp. 1999 Jul; 48(7): 910-4. PMID: 10421235, PII: S0026-0495(99)90228-7, ISSN: 0026-0495.

McGuinness OP, Donmoyer C, Ejiofor J, McElligott S, Lacy DB. Hepatic and muscle glucose metabolism during total parenteral nutrition: impact of infection. Am. J. Physiol. 1998 Nov; 275(5 Pt 1): E763-9. PMID: 9814994, ISSN: 0002-9513.

McGuinness OP, Ejiofor J, Audoly LP, Schrom N. Regulation of glucose production by NEFA and gluconeogenic precursors during chronic glucagon infusion. Am. J. Physiol. 1998 Sep; 275(3 Pt 1): E432-9. PMID: 9725809, ISSN: 0002-9513.

Meinz H, Lacy DB, Ejiofor J, McGuinness OP. Alterations in hepatic gluconeogenic amino acid uptake and gluconeogenesis in the endotoxin treated conscious dog. Shock. 1998 Apr; 9(4): 296-303. PMID: 9565259, ISSN: 1073-2322.

McGuinness OP, Shau V, Benson EM, Lewis M, Snowden RT, Greene JE, Neal DW, Cherrington AD. Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog. Am. J. Physiol. 1997 Oct; 273(4 Pt 1): E674-81. PMID: 9357794, ISSN: 0002-9513.

McGuinness OP, Mari A. Assessment of insulin action on glucose uptake and production during a euglycemic-hyperinsulinemic clamp in dog: a new kinetic analysis. Metab. Clin. Exp. 1997 Oct; 46(10): 1116-27. PMID: 9322792, PII: S0026-0495(97)90202-X, ISSN: 0026-0495.

McGuinness OP, Lacy DB, Ejiofor J, Bagby GG. Hepatic release of tumor necrosis factor in the endotoxin-treated conscious dog. Shock. 1996 May; 5(5): 344-8. PMID: 9156790, ISSN: 1073-2322.

Fujiwara T, Cherrington AD, Neal DN, McGuinness OP. Role of cortisol in the metabolic response to stress hormone infusion in the conscious dog. Metab. Clin. Exp. 1996 May; 45(5): 571-8. PMID: 8622599, PII: S0026-0495(96)90026-8, ISSN: 0026-0495.

McGuinness OP, Lacy DB, Eliasson K. Hyperglucagonemia and hepatic glucose metabolism during infection in the conscious dog. Am. J. Physiol. 1996 Apr; 270(4 Pt 1): E580-8. PMID: 8928762, ISSN: 0002-9513.

McGuinness OP, Jacobs J, Moran C, Lacy B. Impact of infection on hepatic disposal of a peripheral glucose infusion in the conscious dog. Am. J. Physiol. 1995 Aug; 269(2 Pt 1): E199-207. PMID: 7653536, ISSN: 0002-9513.

McGuinness OP, Lacy DB, Anderson J. Effect of acute glucagon removal on metabolic response to infection in conscious dog. Am. J. Physiol. 1995 Jan; 268(1 Pt 1): E92-9. PMID: 7840188, ISSN: 0002-9513.

McGuinness OP. The impact of infection on gluconeogenesis in the conscious dog. Shock. 1994 Nov; 2(5): 336-43. PMID: 7743359, ISSN: 1073-2322.

McGuinness OP, Murrell S, Moran C, Bracy D, Cherrington AD. The effect of acute glucagon removal on the metabolic response to stress hormone infusion in the conscious dog. Metab. Clin. Exp. 1994 Oct; 43(10): 1310-7. PMID: 7934986, PII: 0026-0495(94)90228-3, ISSN: 0026-0495.

McGuinness OP, Burgin K, Moran C, Bracy D, Cherrington AD. Role of glucagon in the metabolic response to stress hormone infusion in the conscious dog. Am. J. Physiol. 1994 Mar; 266(3 Pt 1): E438-47. PMID: 8166265, ISSN: 0002-9513.

McGuinness OP, Fugiwara T, Murrell S, Bracy D, Neal D, O'Connor D, Cherrington AD. Impact of chronic stress hormone infusion on hepatic carbohydrate metabolism in the conscious dog. Am. J. Physiol. 1993 Aug; 265(2 Pt 1): E314-22. PMID: 8368302, ISSN: 0002-9513.

Goldstein RE, Wasserman DH, McGuinness OP, Lacy DB, Cherrington AD, Abumrad NN. Effects of chronic elevation in plasma cortisol on hepatic carbohydrate metabolism. Am. J. Physiol. 1993 Jan; 264(1 Pt 1): E119-27. PMID: 8430780, ISSN: 0002-9513.

Cherrington AD, Pagliassotti MJ, Myers SR, Adkins-Marshall B, McGuinness OP. Factors which regulate net hepatic glucose uptake in vivo. JPEN J Parenter Enteral Nutr. 1991 May; 15(3): 71S-73S. PMID: 1865561, ISSN: 0148-6071.

Myers SR, McGuinness OP, Neal DW, Cherrington AD. Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration. J. Clin. Invest. 1991 Mar; 87(3): 930-9. PMID: 1999501, PMCID: PMC329884, DOI: 10.1172/JCI115100, ISSN: 0021-9738.

Available Postdoctoral Position Details
A postdoctoral position is available for a person interested in the regulation of liver and muscle metabolism in vivo.