Exendin-4 and Liraglutide Attenuate Glucose Toxicity-Induced Cardiac Injury through mTOR/ULK1-Dependent Autophagy

Oxidative Medicine and Cellular Longevity
Wei YuJun Ren

Abstract

Mitochondrial injury and defective autophagy are common in diabetic cardiomyopathy. Recent evidence supports benefits of glucagon-like peptide-1 (GLP-1) agonists exendin-4 (Exe) and liraglutide (LIRA) against diabetic cardiomyopathy. This study was designed to examine the effect of Exe and LIRA on glucose-induced cardiomyocyte and mitochondrial injury, oxidative stress, apoptosis, and autophagy change. Cardiomyocytes isolated from adult mice and H9c2 myoblast cells were exposed to high glucose (HG, 33 mM) with or without Exe or LIRA. Cardiac contractile properties were assessed including peak shortening, maximal velocity of shortening/relengthening (±dL/dt), time to PS, and time-to-90% relengthening (TR90). Superoxide levels, apoptotic proteins such as cleaved caspase-3, Bax, and Bcl-2, and autophagy proteins including Atg5, p62, Beclin-1, LC3B, and mTOR/ULK1 were evaluated using Western blot. Mitochondrial membrane potential (MMP) changes were assessed using JC-1, and autophagosomes were determined using GFP-LC3. Cardiomyocyte exposure to HG exhibited prolonged TR90 associated with significantly decreased PS and ±dL/dt, the effects of which were partly restored by GLP-1 agonists, the effects of which were negated by the mTOR a...Continue Reading

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Citations

Oct 13, 2020·Frontiers in Physiology·Mario SchubertKaomei Guan
Nov 6, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Qun Chen, Edward J Lesnefsky
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Namrita KaurWei Liu
Dec 19, 2020·Chronic Diseases and Translational Medicine·Fan YangDa-Long Zhu
Apr 11, 2021·Ageing Research Reviews·Saikat DewanjeeRamesh Kandimalla
Apr 20, 2021·Oxidative Medicine and Cellular Longevity·Xuwei ZhuChang Jia
Sep 15, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Hai-Peng LiYing-Xin Qi

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Methods Mentioned

BETA
Infection
fluorescence microscopy
protein assay

Software Mentioned

IonOptix SoftEdge
Quantity One

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