Profile

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

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. The microRNA-29 Family Dictates the Balance Between Homeostatic and Pathological Glucose Handling in Diabetes and Obesity. Dooley J, Garcia-Perez JE, Sreenivasan J, Schlenner SM, Vangoitsenhoven R, Papadopoulou AS, Tian L, Schonefeldt S, Serneels L, Deroose C, Staats KA, Van der Schueren B, De Strooper B, McGuinness OP, Mathieu C, Liston A (2016) Diabetes 65(1): 53-61
    › Primary publication · 26696639 (PubMed) · PMC4876765 (PubMed Central)
  2. Enhanced Glucose Transport, but not Phosphorylation Capacity, Ameliorates Lipopolysaccharide-Induced Impairments in Insulin-Stimulated Muscle Glucose Uptake. Otero YF, Mulligan KX, Barnes TM, Ford EA, Malabanan CM, Zong H, Pessin JE, Wasserman DH, McGuinness OP (2016) Shock 45(6): 677-85
    › Primary publication · 26682946 (PubMed) · PMC4868638 (PubMed Central)
  3. The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice. Ceddia RP, Lee D, Maulis MF, Carboneau BA, Threadgill DW, Poffenberger G, Milne G, Boyd KL, Powers AC, McGuinness OP, Gannon M, Breyer RM (2016) Endocrinology 157(1): 220-32
    › Primary publication · 26485614 (PubMed) · PMC4701878 (PubMed Central)
  4. NF-κB-dependent airway inflammation triggers systemic insulin resistance. Cyphert TJ, Morris RT, House LM, Barnes TM, Otero YF, Barham WJ, Hunt RP, Zaynagetdinov R, Yull FE, Blackwell TS, McGuinness OP (2015) Am J Physiol Regul Integr Comp Physiol 309(9): R1144-52
    › Primary publication · 26377563 (PubMed) · PMC4666958 (PubMed Central)
  5. Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex. Kolumam G, Chen MZ, Tong R, Zavala-Solorio J, Kates L, van Bruggen N, Ross J, Wyatt SK, Gandham VD, Carano RA, Dunshee DR, Wu AL, Haley B, Anderson K, Warming S, Rairdan XY, Lewin-Koh N, Zhang Y, Gutierrez J, Baruch A, Gelzleichter TR, Stevens D, Rajan S, Bainbridge TW, Vernes JM, Meng YG, Ziai J, Soriano RH, Brauer MJ, Chen Y, Stawicki S, Kim HS, Comps-Agrar L, Luis E, Spiess C, Wu Y, Ernst JA, McGuinness OP, Peterson AS, Sonoda J (2015) EBioMedicine 2(7): 730-43
    › Primary publication · 26288846 (PubMed) · PMC4534681 (PubMed Central)
  6. Tissue inflammation and nitric oxide-mediated alterations in cardiovascular function are major determinants of endotoxin-induced insulin resistance. House LM, Morris RT, Barnes TM, Lantier L, Cyphert TJ, McGuinness OP, Otero YF (2015) Cardiovasc Diabetol : 56
    › Primary publication · 25986700 (PubMed) · PMC4484635 (PubMed Central)
  7. Interleukin-6 amplifies glucagon secretion: coordinated control via the brain and pancreas. Barnes TM, Otero YF, Elliott AD, Locke AD, Malabanan CM, Coldren AG, Brissova M, Piston DW, McGuinness OP (2014) Am J Physiol Endocrinol Metab 307(10): E896-905
    › Primary publication · 25205821 (PubMed) · PMC4233256 (PubMed Central)
  8. Pathway-selective insulin resistance and metabolic disease: the importance of nutrient flux. Otero YF, Stafford JM, McGuinness OP (2014) J Biol Chem 289(30): 20462-9
    › Primary publication · 24907277 (PubMed) · PMC4110258 (PubMed Central)
  9. Liver but not adipose tissue is responsive to the pattern of enteral feeding. Otero YF, Lundblad TM, Ford EA, House LM, McGuinness OP (2014) Physiol Rep 2(2): e00250
    › Primary publication · 24744913 (PubMed) · PMC3966249 (PubMed Central)
  10. Liver, but not muscle, has an entrainable metabolic memory. Chen SS, Otero YF, Mulligan KX, Lundblad TM, Williams PE, McGuinness OP (2014) PLoS One 9(1): e86164
    › Primary publication · 24465939 (PubMed) · PMC3900485 (PubMed Central)
  11. Cholesteryl ester transfer protein protects against insulin resistance in obese female mice. Cappel DA, Palmisano BT, Emfinger CH, Martinez MN, McGuinness OP, Stafford JM (2013) Mol Metab 2(4): 457-67
    › Primary publication · 24327961 (PubMed) · PMC3854988 (PubMed Central)
  12. A liver Hif-2α-Irs2 pathway sensitizes hepatic insulin signaling and is modulated by Vegf inhibition. Wei K, Piecewicz SM, McGinnis LM, Taniguchi CM, Wiegand SJ, Anderson K, Chan CW, Mulligan KX, Kuo D, Yuan J, Vallon M, Morton LC, Lefai E, Simon MC, Maher JJ, Mithieux G, Rajas F, Annes JP, McGuinness OP, Thurston G, Giaccia AJ, Kuo CJ (2013) Nat Med 19(10): 1331-7
    › Primary publication · 24037094 (PubMed) · PMC3795838 (PubMed Central)
  13. Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets. Reinert RB, Brissova M, Shostak A, Pan FC, Poffenberger G, Cai Q, Hundemer GL, Kantz J, Thompson CS, Dai C, McGuinness OP, Powers AC (2013) Diabetes 62(12): 4154-64
    › Primary publication · 23884891 (PubMed) · PMC3837071 (PubMed Central)
  14. A novel experimental strategy to assess the metabolic effects of selective activation of a G(q)-coupled receptor in hepatocytes in vivo. Li JH, Jain S, McMillin SM, Cui Y, Gautam D, Sakamoto W, Lu H, Jou W, McGuinness OP, Gavrilova O, Wess J (2013) Endocrinology 154(10): 3539-51
    › Primary publication · 23861369 (PubMed) · PMC3776870 (PubMed Central)
  15. Circadian disruption leads to insulin resistance and obesity. Shi SQ, Ansari TS, McGuinness OP, Wasserman DH, Johnson CH (2013) Curr Biol 23(5): 372-81
    › Primary publication · 23434278 (PubMed) · PMC3595381 (PubMed Central)
  16. Inflammation during obesity is not all bad: evidence from animal and human studies. Ye J, McGuinness OP (2013) Am J Physiol Endocrinol Metab 304(5): E466-77
    › Primary publication · 23269411 (PubMed) · PMC3774179 (PubMed Central)
  17. Disassociation of muscle insulin signaling and insulin-stimulated glucose uptake during endotoxemia. Mulligan KX, Morris RT, Otero YF, Wasserman DH, McGuinness OP (2012) PLoS One 7(1): e30160
    › Primary publication · 22276152 (PubMed) · PMC3262801 (PubMed Central)
  18. Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family. Cho SH, Ahn AK, Bhargava P, Lee CH, Eischen CM, McGuinness O, Boothby M (2011) Proc Natl Acad Sci U S A 108(38): 15972-7
    › Primary publication · 21911376 (PubMed) · PMC3179111 (PubMed Central)
  19. Control of muscle glucose uptake: test of the rate-limiting step paradigm in conscious, unrestrained mice. Fueger PT, Shearer J, Bracy DP, Posey KA, Pencek RR, McGuinness OP, Wasserman DH (2005) J Physiol 562(Pt 3): 925-35
    › Primary publication · 15576451 (PubMed) · PMC1665542 (PubMed Central)
  20. Hepatic production and intestinal uptake of IGF-I: response to infection. Lang CH, Frost RA, Ejiofor J, Lacy DB, McGuinness OP (1998) Am J Physiol 275(6 Pt 1): G1291-8
    › Primary publication · 9843765 (PubMed)