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Physiol Rep. 2018 Jul;6(13):e13754. doi: 10.14814/phy2.13754.

Glucagon-like peptide-1 receptor antagonism impairs basal exercise capacity and vascular adaptation to aerobic exercise training in rats.

Author information

1
Division of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado.
2
Department of Medicine, Denver VA Medical Center, University of Colorado School of Medicine, Aurora, Colorado.
3
Division of Bioengineering, University of Colorado School of Medicine, Aurora, Colorado.
4
Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado.

Abstract

Cardiorespiratory fitness (CRF) inversely predicts cardiovascular (CV) mortality and CRF is impaired in people with type 2 diabetes (T2D). Aerobic exercise training (ET) improves CRF and is associated with decreased risk of premature death in healthy and diseased populations. Understanding the mechanisms contributing to ET adaptation may identify targets for reducing CV mortality of relevance to people with T2D. The antihyperglycemic hormone glucagon-like peptide-1 (GLP-1) influences many of the same pathways as exercise and may contribute to CV adaptation to ET. We hypothesized that GLP-1 is necessary for adaptation to ET. Twelve-week-old male Wistar rats were randomized (n = 8-12/group) to receive PBS or GLP-1 receptor antagonist (exendin 9-39 (Ex(9-39)) via osmotic pump for 4 weeks ± ET. CRF was greater with ET (P < 0.01). Ex(9-39) treatment blunted CRF in both sedentary and ET rats (P < 0.001). Ex(9-39) attenuated acetylcholine-mediated vasodilation, while this response was maintained with Ex(9-39)+ET (P = 0.04). Aortic stiffness was greater with Ex(9-39) (P = 0.057) and was made worse when Ex(9-39) was combined with ET (P = 0.004). Ex vivo aortic vasoconstriction with potassium and phenylephrine was lower with Ex(9-39) (P < 0.0001). Carotid strain improved with PBS + ET but did not change in the Ex(9-39) rats with ET (P < 0.0001). Left ventricular mitochondrial respiration was elevated with Ex(9-39) (P < 0.02). GLP-1 receptor antagonism impairs CRF with and without ET, attenuates the vascular adaptation to ET, and elevates cardiac mitochondrial respiration. These data suggest that GLP-1 is integral to the adaptive vascular response to ET.

KEYWORDS:

Aortic strain; mitochondrial respiration; vascular stiffness

PMID:
29984491
PMCID:
PMC6036104
DOI:
10.14814/phy2.13754
[Indexed for MEDLINE]
Free PMC Article

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