Dynamic glucose disposal is driven by reduced endogenous glucose production in response to voluntary wheel running: A stable isotope approach

Allerton, TD, Kowalski, Grzegorz, Hang, H and Stephens, J 2020, Dynamic glucose disposal is driven by reduced endogenous glucose production in response to voluntary wheel running: A stable isotope approach, American Journal of Physiology - Endocrinology and Metabolism, vol. 319, no. 1, pp. E2-E10, doi: 10.1152/ajpendo.00450.2019.

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Title Dynamic glucose disposal is driven by reduced endogenous glucose production in response to voluntary wheel running: A stable isotope approach
Author(s) Allerton, TD
Kowalski, GrzegorzORCID iD for Kowalski, Grzegorz orcid.org/0000-0002-1599-017X
Hang, H
Stephens, J
Journal name American Journal of Physiology - Endocrinology and Metabolism
Volume number 319
Issue number 1
Start page E2
End page E10
Total pages 9
Publisher American Physiological Society
Place of publication Bethesda, Md.
Publication date 2020-07
ISSN 0193-1849
1522-1555
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Physiology
exercise
glucose tolerance
stable isotopes
voluntary wheel running
HIGH-FAT DIET
PYRUVATE-DEHYDROGENASE KINASE-4
TERM HIGH-FAT
INSULIN SENSITIVITY
SKELETAL-MUSCLE
METABOLISM
MICE
RESISTANCE
TOLERANCE
Summary To resolve both the systems level and molecular mechanisms responsible for exercise-induced improvements in glucose tolerance, we sought to test the effect of voluntary wheel running exercise on postprandial glucose dynamics. We utilized a stable isotope-labeled oral glucose tolerance test (SI-OGTT) incorporating complementary deuterium glucose tracers at a 1:1 ratio (2-2H-glucose and 6–6 2H-glucose; 2g/kg lean body mass) to distinguish between endogenous glucose production (EGP) and whole-body glucose disposal. SI-OGTT was performed in C57BL/6J mice after 8 wk on a high-fat diet (HFD; 45% fat). Mice were then randomized to either a wheel-running cage ( n = 13, HFD Ex) or a normal cage ( n = 13, HFD Sed) while maintaining the HFD for 4 wk before performing a SI-OGTT. HFD Ex mice demonstrated improvements in whole blood glucose total area under the curve (AUC) that was attributed primarily to a reduction in EGP AUC. Serum insulin levels measured at 0 and 15 min post- glucose gavage were significantly elevated in the HFD Sed mice, whereas HFD Ex mice demonstrated the expected reduction in insulin at both time points. Overall, exercise improved hepatic insulin sensitivity by reducing postprandial EGP, but also increased whole-body glucose disposal. Finally, these results demonstrate the benefits of exercise on hepatic insulin sensitivity by combining a more physiological route of glucose administration (oral glucose) with the resolution of stable isotope tracers. These novel observations clearly demonstrate that SI-OGTT is a sensitive and cost-effective method to measure exercise adaptations in obese mice with as little as 2 µl of tail blood.
Language eng
DOI 10.1152/ajpendo.00450.2019
Indigenous content off
Field of Research 06 Biological Sciences
11 Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30136861

Document type: Journal Article
Collections: Faculty of Health
School of Exercise and Nutrition Sciences
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