The PPARα/γAgonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat
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METABOLIC FLEXIBILITY WAS ASSESSED IN MALE ZUCKER RATS: lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR) α/γ agonist, tesaglitazar, 3 μ mol/kg/day for 3 weeks. Whole body glucose disposal rate (R d ) and hepatic glucose output (HGO) were assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions using [3,(3)H]glucose. Indices of tissue specific glucose utilization (R g ') were measured at basal, physiological, and supraphysiological levels of insulinemia using 2-deoxy-D-[2,6-(3)H]glucose. Finally, whole body and tissue specific FFA and glucose utilization and metabolic fate were evaluated under basal and hyperinsulinemic conditions using a combination of [U-(13)C]glucose, 2-deoxy-D-[U-(14)C]glucose, [U-(14)C]palmitate, and [9,10-(3)H]-(R)-bromopalmitate. Tesaglitazar improved whole body insulin action by greater suppression of HGO and stimulation of R d compared to obese controls. This involved increased insulin stimulation of R g ' in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (R fa ), and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or R fa compared to obese controls. In conclusion, the results demonstrate that tesaglitazar has a remarkable ability to improve insulin mediated control of glucose and FFA fluxes in obese Zucker rats.
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Tesaglitazar increases whole-body glucose metabolic insulin action in obese rats by reducing hepatic glucose output, restoring skeletal muscle glucose uptake, and suppressing free fatty acid release by adipocytes.
“Tesaglitazar increases whole-body glucose metabolic insulin action in obese rats by reducing hepatic glucose output, restoring skeletal muscle glucose uptake, and suppressing free fatty acid release by adipocytes (272).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [272]
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Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
A RELATION BETWEEN NON-ESTERIFIED FATTY ACIDS IN PLASMA AND THE METABOLISM OF GLUCOSE
Dole, V. P. (1956) · Journal of Clinical Investigation · doi:10.1172/jci103259 · Cited by 3,470 · see citing works
Mechanisms for Insulin Resistance: Common Threads and Missing Links
Samuel, V. T., & Shulman, G. I. (2012) · Cell · doi:10.1016/j.cell.2012.02.017 · Cited by 2,294 · see citing works
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
Kelley, D. E., & Mandarino, L. J. (2000) · Diabetes · doi:10.2337/diabetes.49.5.677 · Cited by 1,017 · see citing works
Morino, K., Petersen, K. F., & Shulman, G. I. (2006) · Diabetes · doi:10.2337/db06-s002 · Cited by 853 · see citing works
Groop, L. C., Bonadonna, R. C., DelPrato, S., Ratheiser, K., Zyck, K., Ferrannini, E., & DeFronzo, R. A. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114142 · Cited by 812 · see citing works
Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue
Kosteli, A., Sugaru, E., Haemmerle, G., Martin, J. F., Lei, J., Zechner, R., & Ferrante, A. W. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42845 · Cited by 726 · see citing works
Estimation of glycogen in small amounts of tissue
Handel, E. V. (1965) · Analytical Biochemistry · doi:10.1016/0003-2697(65)90013-8 · Cited by 560 · see citing works
Metabolic flexibility and insulin resistance
Galgani, J. E., Moro, C., & Ravussin, E. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90558.2008 · Cited by 532 · cited 2× · see citing works
“…August 2013 Academic Editor: Brian Finck Copyright © 2013 Kristina Wallenius et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.”
MethodInfluentialDose-response curves for in vivo insulin sensitivity in individual tissues in rats
Kraegen, E. W., James, D. E., Jenkins, A. B., & Chisholm, D. J. (1985) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1985.248.3.e353 · Cited by 409 · see citing works
Miyazaki, Y., Mahankali, A., Matsuda, M., Glass, L., Mahankali, S., Ferrannini, E., Cusi, K., Mandarino, L. J., & DeFronzo, R. A. (2001) · Diabetes Care · doi:10.2337/diacare.24.4.710 · Cited by 407 · see citing works
Cronet, P., Petersen, J. F. W., Folmer, R. H. A., Blomberg, N., Sjöblom, K., Karlsson, U., Lindstedt, E., & Bamberg, K. (2001) · Structure · doi:10.1016/s0969-2126(01)00634-7 · Cited by 326 · see citing works
Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier
Divakaruni, A. S., Wiley, S. E., Rogers, G. W., Andreyev, A. Y., Petrosyan, S., Loviscach, M., Wall, E. A., Yadava, N., Heuck, A. P., Ferrick, D. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303360110 · Cited by 308 · see citing works
Skeletal muscle fat oxidation: Timing and flexibility are everything
Kelley, D. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25758 · Cited by 298 · see citing works
Mechanisms of the free fatty acid-induced increase in hepatic glucose production
Lam, T. K. T., Carpentier, A. C., Lewis, G. F., van de Werve, G., Fantus, I. G., & Giacca, A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00033.2003 · Cited by 283 · see citing works
Chahil, T. J., & Ginsberg, H. N. (2006) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2006.06.002 · Cited by 233 · see citing works
Free fatty acids and skeletal muscle insulin resistance
Kraegen, E. W., & Cooney, G. J. (2008) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000319118.44995.9a · Cited by 206 · see citing works
Oakes, N. D., Thalén, P., Jacinto, S. M., & Ljung, B. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1158 · Cited by 168 · see citing works
Self-citationInfluence of Plasma Free Fatty Acids on Lipoprotein Synthesis and Diabetic Dyslipidemia
Julius, U. (2003) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2003-41284 · Cited by 131 · see citing works
The role of fibrate treatment in dyslipidemia: an overview
Katsiki, N., Nikolic, D., Montalto, G., Banach, M., Mikhailidis, D. P., & Rizzo, M. (2013) · Current Pharmaceutical Design · doi:10.2174/1381612811319170020 · Cited by 131 · see citing works
Chen, Z., Vigueira, P. A., Chambers, K. T., Hall, A. M., Mitra, M. S., Qi, N., McDonald, W. G., Colca, J. R., Kletzien, R. F., & Finck, B. N. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.363960 · Cited by 121 · see citing works
Fagerberg, B., Edwards, S., Halmos, T., Łopatyński, J., Schuster, H., Stender, S., Birketvedt, G. S., Tonstad, S., Halldórsdóttir, S., & Gause‐Nilsson, I. A. M. (2005) · Diabetologia · doi:10.1007/s00125-005-1846-8 · Cited by 115 · see citing works
Ljung, B., Bamberg, K., Dahllöf, B., Kjellstedt, A., Oakes, N. D., Östling, J., Svensson, L., & Camejo, G. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m200127-jlr200 · Cited by 110 · see citing works
Self-citationGoldstein, B. J., Rosenstock, J., Anzalone, D. A., Tou, C., & Öhman, K. P. (2006) · Current Medical Research and Opinion · doi:10.1185/030079906x154169 · Cited by 70 · see citing works
Derosa, G., & Maffioli, P. (2012) · Current Molecular Pharmacology · doi:10.2174/1874467211205020272 · Cited by 68 · see citing works
Hegarty, B. D., Furler, S. M., Oakes, N. D., Kraegen, E. W., & Cooney, G. J. (2004) · Endocrinology · doi:10.1210/en.2004-0260 · Cited by 66 · see citing works
Self-citationRelation of adipose tissue to metabolic flexibility
Sparks, L. M., Ukropcová, B., Smith, J. M., Pasarica, M., Hymel, D., Xie, H., Bray, G. A., Miles, J. M., & Smith, S. R. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.09.052 · Cited by 61 · see citing works
Bowen, L., Stein, P. P., Stevenson, R. W., & Shulman, G. I. (1991) · Metabolism · doi:10.1016/0026-0495(91)90124-f · Cited by 55 · see citing works
Oakes, N. D., Kjellstedt, A., Forsberg, G., Clementz, T., Camejo, G., Furler, S. M., Kraegen, E. W., Ölwegård-Halvarsson, M., Jenkins, A. B., & Ljung, B. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33520-3 · Cited by 54 · see citing works
Self-citation2-deoxy-d-glucose metabolism in individual tissues of the rat in vivo
Jenkins, A. B., Furler, S. M., & Kraegen, E. W. (1986) · International Journal of Biochemistry · doi:10.1016/0020-711x(86)90036-4 · Cited by 52 · see citing works
Ratner, R. E., Parikh, S. J., & Tou, C. (2007) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2007.042 · Cited by 52 · see citing works
Oakes, N. D., Thalén, P., Aasum, E., Edgley, A. J., Larsen, T. S., Furler, S. M., Ljung, B., & Severson, D. L. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00233.2005 · Cited by 51 · see citing works
Self-citationVaag, A. A., & Beck-Nielsen, H. (1992) · European Journal of Endocrinology · doi:10.1530/acta.0.1270344 · Cited by 45 · see citing works
Chira, E. C., McMillen, T. S., Wang, S., Haw, A., O’Brien, K. D., Wight, T. N., & Chait, A. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.12.012 · Cited by 37 · see citing works
Tesaglitazar, a dual PPARα/γ agonist, ameliorates glucose and lipid intolerance in obese Zucker rats
Oakes, N. D., Thalén, P., Hultstrand, T., Jacinto, S. M., Camejo, G., Wallin, B., & Ljung, B. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00252.2005 · Cited by 36 · see citing works
Self-citationvan der Hoorn, J., Jukema, J. W., Havekes, L. M., Lundholm, E., Camejo, G., Rensen, P. C. N., & Princen, H. M. G. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00109.x · Cited by 33 · see citing works
Schuster, H., Fagerberg, B., Edwards, S., Halmos, T., Łopatyński, J., Stender, S., Birketvedt, G. S., Tonstad, S., Gause‐Nilsson, I. A. M., Halldórsdóttir, S., et al. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.05.029 · Cited by 31 · see citing works
Keil, S., Müller, M., Zoller, G., Haschke, G., Schroeter, K., Glien, M., Ruf, S. G., Focken, I., Herling, A. W., & Schmoll, D. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm101179e · Cited by 27 · see citing works
Roles of Fatty Acid Oversupply and Impaired Oxidation in Lipid Accumulation in Tissues of Obese Rats
Oakes, N. D., Kjellstedt, A., Thalén, P., Ljung, B., & Turner, N. A. (2013) · Journal of Lipids · doi:10.1155/2013/420754 · Cited by 20 · see citing works
Self-citationDavoren, P. M., Kelly, W., Gries, F. A., Hübinger, A., Whately‐Smith, C., & Alberti, K. G. M. M. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90252-9 · Cited by 17 · see citing works
van der Hoorn, J. W., Jukema, J. W., Havekes, L. M., et al. (2008) · Atherosclerosis Supplements · doi:10.1016/s1567-5688(08)70837-7 · Cited by 15 · see citing works
Effect of insulin on [3H]deoxy-D-glucose pharmacokinetics in the rat
Furler, S. M., Jenkins, A. B., & Kraegen, E. W. (1988) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1988.255.6.e806 · Cited by 14 · see citing works
Fagerberg, B., Schuster, H., Birketvedt, G. S., et al. (2007) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2007.038 · Cited by 7 · see citing works
Oakes, N. D., Ljung, B., & Camejo, G. (2002) · Europe PMC (PubMed Central) · Cited by 5 · see citing works
Self-citationRandle (1998) · doi:10.1002/(sici)1099-0895(199812)14:4
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Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
- Authors
- Wallenius, K., Kjellstedt, A., Thalén, P., Löfgren, L., & Oakes, N. D.
- Affiliations
- AstraZeneca (Sweden) (SE)
- Corresponding author
- Wallenius, Kristina
- Venue
- PPAR Research
- Publisher
- Wiley
- Published
- 2013
- Volume
- 2013
- Pages
- 1-14
- ISSN
- 1687-4757 (ISSN-L)
- 1687-4765
- PMC
- PMC3826326
- OpenAlex
- W2162264116
- Cited by
- 22
- References
- 45
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PPAR Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- tesaglitazar, insulin sensitivity, metabolic flexibility, glucose utilization, hepatic glucose production, glucose disposal rate, glycogen synthesis, skeletal muscle, adipose tissue, hyperinsulinemic-euglycemic clamp, Zucker fatty rats, insulin resistance
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