Liraglutide Improves the Survival of INS-1 Cells by Promoting Macroautophagy

Yin, Jia Jing; Li, Yan Bo; Cao, Ming; Wang, Yan

doi:10.5812/ijem.8088

Cited by 26 publications

(23 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, Sharma et al demonstrated that GLP-1 reduced the fat load in hepatocytes by increasing the rate of autophagosome and autophagolysosome formation, i.e., autophagic flux [ 37 ]. Consistent with a previous study, autophagy has been reported to play a protective role in PA-induced cell death and alleviate the lipid burden in INS-1 cells [ 38 ]. Thus, we confirmed that palmitate induced autophagy in rat insulin-secreting cells, which is related to the pathogenesis of T2D.…”

Section: Discussionsupporting

confidence: 91%

Interleukin-22 Alleviated Palmitate-Induced Endoplasmic Reticulum Stress in INS-1 Cells through Activation of Autophagy

Yang

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

ObjectiveStimulation with saturated fatty acids has been shown to induce oxidative stress and endoplasmic reticulum (ER) stress in β cells and has been recognized as an important component of the pathogenesis of type 2 diabetes (T2D). Interleukin-22 (IL-22) plays a critical role in preventing β cells from oxidative and ER stress, and autophagy is associated with the survival and function of β cells. However, whether IL-22 alleviates cellular stress through activation of autophagy is unclear. In this study, we investigated the effects of IL-22 on rat insulin-secreting cells and the mechanisms underlying IL-22 and lipotoxicity-induced oxidative and ER stress in vitro.MethodsThe levels of reactive oxygen species (ROS) were detected by flow cytometry and fluorescence microscopy. The protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), microtubule-associated protein light chain 3B (LC3B) and Bcl-2-interacting myosin-like coiled-coil protein (Beclin-1) were evaluated by western blot. Transmission electron microscopy was utilized to observe the process of autophagy.ResultsPalmitate induced increased levels of ROS and the overexpression of GRP78 and CHOP, whereas these effects were partly reversed by treatment with IL-22. Furthermore, IL-22 upregulated the protein expression of Beclin-1 and the conversion of LC3B-I to LC3B-II. Moreover, the aforementioned effects were partly suppressed by treating cells with 3-methyladenine (3-MA), an autophagy inhibitor.ConclusionsOur results suggest that IL-22 alleviated the oxidative and ER stress induced by palmitate, which was likely mediated by autophagy. These findings could facilitate the development of novel therapeutic strategies to suppress the progression of T2D.

show abstract

Section: Discussionsupporting

confidence: 91%

Interleukin-22 Alleviated Palmitate-Induced Endoplasmic Reticulum Stress in INS-1 Cells through Activation of Autophagy

Yang

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Recently, liraglutide has been shown to protect against NAFLD in both human trials and cellular models . Throughout these investigations, liraglutide has been demonstrated to have lots of effects, including enhancing cell survival through promoting autophagy, inhibition of inflammation, attenuation of endoplasmic reticulum stress and so on; however, the precise molecular mechanisms are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Liraglutide ameliorates non‐alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3–FOXO3a pathway

Tong

Qiu

et al. 2016

Hepatology Research

View full text Add to dashboard Cite

show abstract

“…Third, activation of the glucagon-like peptide-1 (GLP-1) receptor or treatment with a DDP-4 inhibitor triggers AMP-activated protein kinase (AMPK) signaling [ 22 , 23 , 24 ], which facilitates autophagy [ 5 , 9 , 15 , 18 , 25 ]. In fact, a GLP-1 analog, liraglutide, has been shown to promote autophagy in non-cardiac cells [ 26 ]. Fourth, it has been reported that the activity of circulating DPP-4 is associated with left ventricular dysfunction in patients [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats

Murase

Kuno

Miki

et al. 2015

Cardiovasc Diabetol

View full text Add to dashboard Cite

BackgroundType 2 diabetes mellitus (T2DM) worsens the outcome after myocardial infarction (MI). Here, we hypothesized that inhibition of dipeptidyl peptidase-4 (DPP-4) improves survival after MI in T2DM by modifying autophagy in the non-infarcted region of the heart.Methods and resultsUnder baseline conditions, there was no significant difference between levels of myocardial autophagy marker proteins in OLETF, a rat model of T2DM, and in LETO, a non-diabetic control. However, in contrast to the response in LETO, LC3-II protein and LC3-positive autophagosomes in the non-infarcted region of the myocardium were not increased after MI in OLETF. The altered autophagic response in OLETF was associated with lack of AMPK/ULK-1 activation, attenuated response of Akt/mTOR/S6 signaling and increased Beclin-1–Bcl-2 interaction after MI. Treatment with vildagliptin (10 mg/kg/day s.c.), a DPP-4 inhibitor, suppressed Beclin-1–Bcl-2 interaction and increased both LC3-II protein level and autophagosomes in the non-infarcted region in OLETF, though it did not normalize AMPK/ULK-1 or mTOR/S6 signaling. Plasma insulin level, but not glucose level, was significantly reduced by vildagliptin at the dose used in this study. Survival rate at 48 h after MI was significantly lower in OLETF than in LETO (32 vs. 82%), despite similar infarct sizes. Vildagliptin improved the survival rate in OLETF to 80%, the benefit of which was abrogated by chloroquine, an autophagy inhibitor.ConclusionsThe results indicate that vildagliptin reduces T2DM-induced increase in post-MI acute mortality possibly by restoring the autophagic response through attenuation of Bcl-2-Beclin-1 interaction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0264-6) contains supplementary material, which is available to authorized users.

show abstract

Liraglutide Improves the Survival of INS-1 Cells by Promoting Macroautophagy

Cited by 26 publications

References 26 publications

Interleukin-22 Alleviated Palmitate-Induced Endoplasmic Reticulum Stress in INS-1 Cells through Activation of Autophagy

Interleukin-22 Alleviated Palmitate-Induced Endoplasmic Reticulum Stress in INS-1 Cells through Activation of Autophagy

Liraglutide ameliorates non‐alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3–FOXO3a pathway

Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats

Contact Info

Product

Resources

About