NO-Dependent Akt Inactivation by S-Nitrosylation as a Possible Mechanism of STZ-Induced Neuronal Insulin Resistance

2018 ◽  
Vol 65 (4) ◽  
pp. 1427-1443 ◽  
Author(s):  
Fernanda Crunfli ◽  
Caio Henrique Mazucanti ◽  
Ruan Carlos Macêdo de Moraes ◽  
Andressa Pereira Costa ◽  
Alice Cristina Rodrigues ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Neuronal Insulin Resistance

scholarly journals Liraglutide Suppresses Tau Hyperphosphorylation, Amyloid Beta Accumulation through Regulating Neuronal Insulin Signaling and BACE-1 Activity

2020 ◽  
Vol 21 (5) ◽  
pp. 1725 ◽  
Author(s):  
Salinee Jantrapirom ◽  
Wutigri Nimlamool ◽  
Nipon Chattipakorn ◽  
Siriporn Chattipakorn ◽  
Piya Temviriyanukul ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glycogen Synthase ◽  
Insulin Receptors ◽  
Beta Amyloid ◽  
Significant Feature ◽  
Amyloid Formation ◽  
Tau Hyperphosphorylation ◽  
Insulin Resistant ◽  
Neuronal Insulin Resistance ◽  
Bace 1

Neuronal insulin resistance is a significant feature of Alzheimer’s disease (AD). Accumulated evidence has revealed the possible neuroprotective mechanisms of antidiabetic drugs in AD. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog and an antidiabetic agent, has a benefit in improving a peripheral insulin resistance. However, the neuronal effect of liraglutide on the model of neuronal insulin resistance with Alzheimer’s formation has not been thoroughly investigated. The present study discovered that liraglutide alleviated neuronal insulin resistance and reduced beta-amyloid formation and tau hyperphosphorylation in a human neuroblostoma cell line, SH-SY5Y. Liraglutide could effectively reverse deleterious effects of insulin overstimulation. In particular, the drug reversed the phosphorylation status of insulin receptors and its major downstream signaling molecules including insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK-3β). Moreover, liraglutide reduced the activity of beta secretase 1 (BACE-1) enzyme, which then decreased the formation of beta-amyloid in insulin-resistant cells. This indicated that liraglutide can reverse the defect of phosphorylation status of insulin signal transduction but also inhibit the formation of pathogenic Alzheimer’s proteins like Aβ in neuronal cells. We herein provided the possibility that the liraglutide-based therapy may be able to reduce such deleterious effects caused by insulin resistance. In view of the beneficial effects of liraglutide administration, these findings suggest that the use of liraglutide may be a promising therapy for AD with insulin-resistant condition.

scholarly journals Excitotoxic glutamate causes neuronal insulin resistance by inhibiting insulin receptor/Akt/mTOR pathway

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Igor Pomytkin ◽  
Irina Krasil’nikova ◽  
Zanda Bakaeva ◽  
Alexander Surin ◽  
Vsevolod Pinelis
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Cortical Neurons ◽  
Glycogen Synthase ◽  
Primary Cultures ◽  
Biological Response ◽  
Mtor Pathway ◽  
Serine Phosphorylation ◽  
Glutamate Excitotoxicity ◽  
Neuronal Insulin Resistance

Abstract Aim An impaired biological response to insulin in the brain, known as central insulin resistance, was identified during stroke and traumatic brain injury, for which glutamate excitotoxicity is a common pathogenic factor. The exact molecular link between excitotoxicity and central insulin resistance remains unclear. To explore this issue, the present study aimed to investigate the effects of glutamate-evoked increases in intracellular free Ca2+ concentrations [Ca2+]i and mitochondrial depolarisations, two key factors associated with excitotoxicity, on the insulin-induced activation of the insulin receptor (IR) and components of the Akt/ mammalian target of rapamycin (mTOR) pathway in primary cultures of rat cortical neurons. Methods Changes in [Ca2+]i and mitochondrial inner membrane potentials (ΔΨm) were monitored in rat cultured cortical neurons, using the fluorescent indicators Fura-FF and Rhodamine 123, respectively. The levels of active, phosphorylated signalling molecules associated with the IR/Akt/mTOR pathway were measured with the multiplex fluorescent immunoassay. Results When significant mitochondrial depolarisations occurred due to glutamate-evoked massive influxes of Ca2+ into the cells, insulin induced 48% less activation of the IR (assessed by IR tyrosine phosphorylation, pY1150/1151), 72% less activation of Akt (assessed by Akt serine phosphorylation, pS473), 44% less activation of mTOR (assessed by mTOR pS2448), and 38% less inhibition of glycogen synthase kinase β (GSK3β) (assessed by GSK3β pS9) compared with respective controls. These results suggested that excitotoxic glutamate inhibits signalling via the IR/Akt/mTOR pathway at multiple levels, including the IR, resulting in the development of acute neuronal insulin resistance within minutes, as an early pathological event associated with excitotoxicity.

Effects of estrogen in preventing neuronal insulin resistance in hippocampus of obese rats are different between genders

Life Sciences ◽  
2011 ◽  
Vol 89 (19-20) ◽  
pp. 702-707 ◽  
Author(s):  
Wasana Pratchayasakul ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Insulin Resistance ◽  
Obese Rats ◽  
Neuronal Insulin Resistance

scholarly journals PPARγ Agonist Improves Neuronal Insulin Receptor Function in Hippocampus and Brain Mitochondria Function in Rats with Insulin Resistance Induced by Long Term High-Fat Diets

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 329-338 ◽  
Author(s):  
Noppamas Pipatpiboon ◽  
Wasana Pratchayasakul ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Insulin Resistance ◽  
Conformational Changes ◽  
Brain Mitochondria ◽  
Normal Diet ◽  
High Fat ◽  
Long Term Depression ◽  
Peripheral Insulin Resistance ◽  
Pparγ Agonist ◽  
Neuronal Insulin Resistance

We previously demonstrated that a high-fat diet (HFD) consumption can cause not only peripheral insulin resistance, but also neuronal insulin resistance. Moreover, the consumption of an HFD has been shown to cause mitochondrial dysfunction in both the skeletal muscle and liver. Rosiglitazone, a peroxizome proliferator-activated receptor-γ ligand, is a drug used to treat type 2 diabetes mellitus. Recent studies suggested that rosiglitazone can improve learning and memory in both human and animal models. However, the effects of rosiglitazone on neuronal insulin resistance and brain mitochondria after the HFD consumption have not yet been investigated. Therefore, we tested the hypothesis that rosiglitazone improves neuronal insulin resistance caused by a HFD via attenuating the dysfunction of neuronal insulin receptors and brain mitochondria. Rosiglitazone (5 mg/kg · d) was given for 14 d to rats that were fed with either a HFD or normal diet for 12 wk. After the 14th week, all animals were euthanized, and their brains were removed and examined for insulin-induced long-term depression, neuronal insulin signaling, and brain mitochondrial function. We found that rosiglitazone significantly improved peripheral insulin resistance and insulin-induced long-term depression and increased neuronal Akt/PKB-ser phosphorylation in response to insulin. Furthermore, rosiglitazone prevented brain mitochondrial conformational changes and attenuated brain mitochondrial swelling, brain mitochondrial membrane potential changes, and brain mitochondrial ROS production. Our data suggest that neuronal insulin resistance and the impairment of brain mitochondria caused by a 12-wk HFD consumption can be reversed by rosiglitazone.

scholarly journals P2-249: Neuronal insulin resistance reduces Alzheimer-like pathology in Tg2576 mice independent of Foxo1 mediated transcription

2011 ◽  
Vol 7 ◽  
pp. S391-S391
Author(s):  
Lorna Moll ◽  
Katharina Schilbach ◽  
Oliver Stöhr ◽  
Michael Udelhoven ◽  
Johanna Zemva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Neuronal Insulin Resistance ◽  
Tg2576 Mice

scholarly journals Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer’s Disease

2017 ◽  
Vol 58 (4) ◽  
pp. 1151-1161 ◽  
Author(s):  
Norimichi Nakamura ◽  
Yasumasa Ohyagi ◽  
Tomohiro Imamura ◽  
Yuki T. Yanagihara ◽  
Kyoko M. Iinuma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Neuronal Insulin Resistance
Sign in / Sign up

Export Citation Format

Share Document