The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1α/CXCR4 pathway

Cardiovascular Diabetology
Fausto ChiazzaCesare Patrone

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are approved drugs for the treatment of hyperglycemia in patients with type 2 diabetes. These effects are mainly mediated by inhibiting endogenous glucagon-like peptide-1 (GLP-1) cleavage. Interestingly, gliptins can also improve stroke outcome in rodents independently from GLP1. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist promoting beneficial effects in injured brains. However, SDF-1α involvement in gliptin-mediated neuroprotection after ischemic injury is unproven. We aimed to determine whether the gliptin linagliptin improves stroke outcome via the SDF-1α/CXCR4 pathway, and identify additional effectors behind the efficacy. Mice were subjected to stroke by transient middle cerebral artery occlusion (MCAO). linagliptin was administered for 3 days or 3 weeks from stroke onset. The CXCR4-antagonist AMD3100 was administered 1 day before MCAO until 3 days thereafter. Stroke outcome was assessed by measuring upper-limb function, infarct volume and neuronal survival. The plasma and brain levels of active GLP-1, GIP and SDF-1α were quantified by ELISA. To identify additional gliptin-mediated molecul...Continue Reading

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Citations

Feb 7, 2019·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Dimitrios MilonasKonstantinos Tziomalos
Apr 3, 2019·Brain Injury : [BI]·Damla ErbilHale Yapıcı Eser
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Feb 18, 2020·Pharmacology & Therapeutics·Shiying ShaoYong Chen
Nov 6, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Feng-Li HaoXiong-Fei Zhao
Jun 8, 2019·Metabolism: Clinical and Experimental·Olivia M FarrChristos S Mantzoros

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay

Clinical Trials Mentioned

NCT01897532

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