Dynamic glucose disposal is driven by reduced endogenous glucose production in response to voluntary wheel running: a stable isotope approach
- 27 April 2020
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 319 (1), E2-E10
- https://doi.org/10.1152/ajpendo.00450.2019
Abstract
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-H-2-glucose and 6-6 H-2-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 mu l of tail blood.Keywords
Funding Information
- Office of Dietary Supplements (P50AT002776)
- HHS | NIH | National Center for Complementary and Integrative Health (AT004094)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (DK052968)
This publication has 47 references indexed in Scilit:
- Genetic Inactivation of Pyruvate Dehydrogenase Kinases Improves Hepatic Insulin Resistance Induced DiabetesPLOS ONE, 2013
- Effects of high-fat diet and physical activity on pyruvate dehydrogenase kinase-4 in mouse skeletal muscleNutrition & Metabolism, 2012
- Wheel Access Does Not Attenuate Weight Gain in Mice Fed High-Fat or High-CHO DietsMedicine & Science in Sports & Exercise, 2010
- Advantages of dynamic “closed loop” stable isotope flux phenotyping over static “open loop” clamps in detecting silent genetic and dietary phenotypesMetabolomics, 2009
- Regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) gene expression by glucocorticoids and insulinMolecular and Cellular Endocrinology, 2009
- Glycogen storage and muscle glucose transporters (GLUT-4) of mice selectively bred for high voluntary wheel runningJournal Of Experimental Biology, 2009
- Pyruvate dehydrogenase kinase-4 deficiency lowers blood glucose and improves glucose tolerance in diet-induced obese miceAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Effect of the volume and intensity of exercise training on insulin sensitivityJournal of Applied Physiology, 2004
- Effect of Voluntary Wheel-Running on Insulin Sensitivity and Responsiveness in High-Fat-Fed Rats.Endocrine Journal, 2001
- Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load.JCI Insight, 1988