Protective effect of liraglutide against ER stress in the liver of high-fat diet-induced insulin-resistant rats

Yang, Jing; Ao, Na; Du, Juan; Wang, Xiaochen; He, Yan-Ling

doi:10.1007/s12020-014-0480-y

Cited by 22 publications

(23 citation statements)

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“…This is the first time to prove that exenatide ameliorates lipid‐induced hepatic ER stress to improve lipid deposition in hepatocytes both in vivo and in vitro . In support of our findings, a previous study showed that liraglutide protected against ER stress in the livers of HFD‐induced insulin‐resistant rats . These findings collectively reveal the ability of GLP‐1 receptor agonists to protect against ER stress and hepatic steatosis.…”

Section: Discussionsupporting

confidence: 91%

“…In support of our findings, a previous study showed that liraglutide protected against ER stress in the livers of HFD-induced insulin-resistant rats. (32) These findings collectively reveal the ability of GLP-1 receptor agonists to protect against ER stress and hepatic steatosis. Moreover, our study validated that exenatide (exendin-4) alleviated hepatic ER stress in a SIRT1-dependent manner by using genetic or pharmacological SIRT1 inhibition both in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 87%

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SIRT1/HSF1/HSP pathway is essential for exenatide‐alleviated, lipid‐induced hepatic endoplasmic reticulum stress

Zheng¹,

Xu²,

Liang³

et al. 2017

Hepatology

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 87%

SIRT1/HSF1/HSP pathway is essential for exenatide‐alleviated, lipid‐induced hepatic endoplasmic reticulum stress

Zheng¹,

Xu²,

Liang³

et al. 2017

Hepatology

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“…Stimulation of glucagon‐like peptide‐1 (GLP‐1) receptor by a GLP‐1 analogue can activate AMPKα and suppress ER stress (Shao et al , ; Yang et al , ). Furthermore, there is considerable evidence for an important role of GLP‐1R in cardiovascular actions.…”

Section: Introductionmentioning

confidence: 99%

Protection against cardiac hypertrophy by geniposide involves the GLP‐1 receptor / AMPKα signalling pathway

Dai

Zhang

et al. 2016

British J Pharmacology

105

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BACKGROUND AND PURPOSEActivation of glucagon-like peptide-1 (GLP-1) receptor exerts a range of cardioprotective effects. Geniposide is an agonist of GLP-1 receptor, but its role in cardiac hypertrophy remains completely unknown. Here, we have investigated its protective effects and clarified the underlying molecular mechanisms. EXPERIMENTAL APPROACHThe transverse aorta was constricted in C57/B6 mice and then geniposide was given orally for 7 weeks. Morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers were used to evaluate hypertrophy. KEY RESULTSGeniposide inhibited the hypertrophic response induced by constriction of the transverse aorta or by isoprenaline. Activation of 5′-AMP-activated protein kinase-α (AMPKα) and inhibition of mammalian target of rapamycin, ERK and endoplasmic reticulum stress were observed in hypertrophic hearts that were treated with geniposide. Furthermore, Compound C (CpC) or knock-down of AMPKα restricted protection of geniposide against cell hypertrophy and activation of mammalian target of rapamycin and ERK induced by hypertrophic stimuli. CpC or shAMPKα also abolished the protection of geniposide against endoplasmic reticulum stress induced by thapsigargin or dihtiothreitol. The cardio-protective effects of geniposide were ablated in mice subjected to CpC. GLP-1receptor blockade counteracted the anti-hypertrophic response and activation of AMPKα by geniposide. Knock-down of GLP-1 receptor also offset the inhibitory effects of geniposide on cardiac hypertrophy in vivo. CONCLUSIONS AND IMPLICATIONSGeniposide protected against cardiac hypertrophy via activation of the GLP-1 receptor/AMPKα pathway. Geniposide is a potential therapeutic drug for cardiac hypertrophy. AbbreviationsAICAR, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside; AMPK, 5′-AMP-activated protein kinase; Ang, angiotensin; ANP, atrial natriuretic peptide; CpC, Compound C; CSA, cross-sectional area; Ex, Exendin; FS, fractional shortening; GE, geniposide; GLP, glucagon-like peptide; HW/BW, heart weight/body weight; HW/TL, heart weight/tibia length; LVIDd, left ventricular internal diastolic diameter; mTOR, mammalian target of rapamycin; TAC, constriction of the transverse aorta; TG, thapsigargin; β-MHC, β-myosin heavy chain IntroductionCardiac hypertrophy is characterized by enlargement of the heart and is the response of the heart to a variety of stimuli (Tang et al., 2009). It can progress to heart failure, and ultimately leads to high rates of mortality and morbidity (Shah and Mann, 2011). Although considerable progress has been made in understanding the molecular mechanisms underlying hypertrophy, drugs that constrain these pathways are yet to be discovered. One of the mechanisms that could promote cardiac hypertrophy is endoplasmic reticulum (ER) stress. Once ER stress is activated, branches of the protein response increase ROS and induce apotosis, contributing to the process of cardiac hypertrophy (McCullough et al., 2001;Harding et al., 2003). Therefore, it is of im...

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“…Chen et al showed that liraglutide can improve glucose metabolism and insulin resistance in diabetic KKAy mice by stimulating insulin secretion, increasing glycogen production and glycolysis, and up-regulating GLUT4 expression [32]. Numerous studies have shown that endoplasmic reticulum stress is an important pathway for the induction and development of insulin resistance, and previous studies have confirmed the inevitable role of GLP-1 analogues in combating insulin resistance and endoplasmic reticulum stress [33]. In addition, studies have shown that weight loss can improve insulin resistance, reduce insulin secretion requirements, and may improve the effects of glucose and lipotoxicity on pancreatic beta cells [34].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the effect of liraglutide on glycemic variability in patients with type 2 diabetes

et al. 2020

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The efficacy of liraglutide in the treatment of glycemic variability in type 2 diabetic patients remains to be fully elucidated. Some studies evaluated the efficacy and safety of liraglutide in glycemic variability, and this meta-analysis was performed to evaluate the accuracy of the results of existing studies on the efficacy of liraglutide. We conducted a comprehensive search for all relevant studies published in PubMed, EMBASE, Cochrane Library, and China Academic Journal Full-Text Database from the beginning of 2011 to October 31, 2019. The mean ± SD and 95% confidence interval were used for evaluation, and subgroup and sensitivity analysis were carried out. Publication bias was estimated by funnel plots and Egger's tests. A total of 16 studies were included in the meta-analysis involving 492 participants. MAGE (mean amplitude of glycemic excursion), LAGE (largest amplitude of glycemic excursions), SD (standard deviation of blood glucose), and MODD (mean of daily differences) were collected to reflect the variability of blood glucose. The glycemic variability indexes of patients before and after treatment with liraglutide were compared. Patients with treatment had lower glycemic variability compared with patients receiving treatment of liraglutide. Compared with the patients before the treatment, the patients after the treatment had a smaller glycemic variability (MAGE: I 2 = 92%, p < 0.01, Z = 11.91, p < 0.01, MD = -2.78, 95%CI: -3.24 --2.32; LAGE: I 2 = 76%, p = 0.08, Z = 9.94, p < 0.01, MD = -2.20, 95%CI: -2.59 --1.81; MODD: I 2 = 74%, p = 0.002, Z = 14.03, p < 0.01, MD = -0.90, 95%CI: -1.02 --0.77; SD: I 2 = 93%, p < 0.01, Z = 3.62, p < 0.01, SMD = -1.77, 95%CI: -2.73 --0.81). Sensitivity analysis showed that our results were reliable and no evidence of significant publication bias was detected. The results of this study suggest that patients with type 2 diabetes treated with liraglutide are associated with lower glycemic variability.

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Protective effect of liraglutide against ER stress in the liver of high-fat diet-induced insulin-resistant rats

Cited by 22 publications

References 41 publications

SIRT1/HSF1/HSP pathway is essential for exenatide‐alleviated, lipid‐induced hepatic endoplasmic reticulum stress

SIRT1/HSF1/HSP pathway is essential for exenatide‐alleviated, lipid‐induced hepatic endoplasmic reticulum stress

Protection against cardiac hypertrophy by geniposide involves the GLP‐1 receptor / AMPKα signalling pathway

Analysis of the effect of liraglutide on glycemic variability in patients with type 2 diabetes

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