Liraglutide ameliorates cognitive decline by promoting autophagy via the AMP-activated protein kinase/mammalian target of rapamycin pathway in a streptozotocin-induced mouse model of diabetes

Kong, Fanhua; Wu, Jiahua; Sun, Shuiya; Ma, Liang; Zhou, Jiaheng

doi:10.1016/j.neuropharm.2018.01.001

Cited by 55 publications

(30 citation statements)

References 58 publications

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“…Moreover, the mTOR signaling pathway has been shown to be involved in regulating neuronal function, proliferation, apoptosis, and other cellular processes associated with epileptogenesis. Studies have shown that the activity of the mTOR signaling pathway is abnormally increased in epilepsy models, and that GLP-1 analogs can regulate mTOR expression via the AMPK pathway (Hurtado-Carneiro et al, 2012;Kong et al, 2018). In our experiments, we found that apoptosis and mTOR expression were increased in Scn1a KO mice and cell models.…”

Section: Discussionsupporting

confidence: 58%

The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

et al. 2020

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Moreover, liraglutide protected against Scn1a KO-induced apoptosis, which was manifested in the phosphorylation of mTOR (KO+NS: 1.99 ± 0.31 vs. KO+Lira: 0.97 ± 0.18, P = 0.0004), as well as the downregulation of cleaved caspase-3 (KO+NS: 0.49 ± 0.04 vs. KO+Lira: 0.30 ± 0.01, P = 0.0003) and restoration of the imbalance between BAX (KO+NS: 0.90 ± 0.02 vs. KO +Lira: 0.75 ± 0.04, P = 0.0005) and BCL-2 (KO+NS: 0.46 ± 0.02 vs. KO+Lira: 0.61 ± 0.02, P = 0.0006). Collectively, these results show that liraglutide reduces seizure susceptibility and cognitive dysfunction in the mouse model of Dravet syndrome, and exerts anti-apoptotic and neuroprotective effects in Scn1a KO mice and cells.

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Section: Discussionsupporting

confidence: 58%

The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

et al. 2020

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“… Lin et al (2018) found a higher autophagy level in rats with STZ-induced diabetes. Previous studies found that liraglutide relieved cognitive decline and myocardial damage by promoting autophagy via the AMP-activated protein kinase/mammalian target of rapamycin pathway ( Zhang et al, 2017 ; Kong et al, 2018b ). Based on these, we examined the expression of autophagy markers in the corpus cavernosal tissue and CCSMCs to expound the role of autophagy in the protective effect of liraglutide,.…”

Section: Discussionmentioning

confidence: 99%

Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus

Yuan

Gao

et al. 2020

Front. Pharmacol.

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Background: Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro. Methods: Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Erectile function was assessed by cavernous nerve electrostimulation. The corpus cavernosum was used for further study. In vitro, effects of liraglutide were evaluated by primary corpus cavernosum smooth muscle cells (CCSMCs) exposed to low or high glucose (HG)containing medium with or without liraglutide and GLP-1 receptor (GLP-1R) inhibitor. Western blotting, fluorescent probe, immunohistochemistry, and relevant assay kits were performed to measure the levels of target proteins. Results: Administration of liraglutide did not significantly affect plasma glucose and body weights in diabetic rats, but improved erectile function, reduced levels of NADPH oxidases and ROS production, downregulated expression of Ras homolog gene family (RhoA) and Rho-associated protein kinase (ROCK) 2 in the DMED group dramatically. The liraglutide treatment promoted autophagy further and restored expression of GLP-1R in the DMED group. Besides, cultured CCSMCs with liraglutide exhibited a lower level of oxidative stress accompanied by inhibition of the RhoA/ROCK pathway and a higher level of autophagy compared with HG treatment. These beneficial effects of liraglutide effectively reversed by GLP-1R inhibitor. Conclusion: Liraglutide exerts protective effects on ED associated with the regulation of smooth muscle dysfunction, oxidative stress and autophagy, independently of a glucose

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“…In the present study, fasting blood glucose levels before the experiment, at 72 hours post STZ injection and at the end of the experiment were measured by enzymatic GOD‐PAP (glucose oxidase peroxidase) diagnostic kits. The rats were considered to be diabetic if their fasting blood glucose levels exceeded 16.7 mmol/L . The rest 70 successful rat models were further randomly divided into the following five groups with 14 animals in each: (a) DM group (DM); (b) DM +NC group, the rats treated with NC (100 mg/kg/body weight); (c3) DM + RAP (RAP) group (1 mg/kg body weight); (d) DM + NC (100 mg/kg body weight) + CQ (40 mg/kg body weight); (e) DM + NC (100 mg/kg body weight) + 3‐MA (1.5 mg/kg body weight).…”

Section: Methodsmentioning

confidence: 99%

“…The rats were considered to be diabetic if their fasting blood glucose levels exceeded 16.7 mmol/L . 23 The rest 70 successful rat models were further randomly divided into the following five groups with 14 ani-…”

Section: Model Building and Animal Groupingmentioning

confidence: 99%

Nicotinate‐curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus

Tang

et al. 2018

CNS Neurosci Ther

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Liraglutide ameliorates cognitive decline by promoting autophagy via the AMP-activated protein kinase/mammalian target of rapamycin pathway in a streptozotocin-induced mouse model of diabetes

Cited by 55 publications

References 58 publications

The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus

Nicotinate‐curcumin ameliorates cognitive impairment in diabetic rats by rescuing autophagic flux in CA1 hippocampus

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