Cited by 22Peroxisome Proliferator-Activated ReceptorsAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

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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Wallenius, Kristina, Kjellstedt, Ann, Thalén, Pia, Löfgren, Lars, Oakes, Nicholas D.·2013·PPAR Research

Abstract

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).”

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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
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
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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