Insulin-like growth factor-1 activates AMPK to augment mitochondrial function and correct neuronal metabolism in sensory neurons in type 1 diabetes

Aghanoori, Mohamad‐Reza; Smith, Daniel R.; Shariati-Ievari, Shiva; Ajisebutu, Andrew; Nguyen, Annee; Desmond, Fiona; Jesus, Carlos Henrique Alves; Zhou, Xiajun; Calcutt, Nigel A.; Aliani, Michel; Fernyhough, Paul

doi:10.1016/j.molmet.2018.11.008

Cited by 53 publications

(46 citation statements)

References 86 publications

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“…18 AMPK induced by insulin-like growth factor-1 improved mitochondrial function to drive axonal outgrowth. 46 Under stress conditions such as energy depletion, the AMPK F I G U R E 5 ANXA1 promoted SC proliferation and remyelination in vivo. A, Representative images of the immunofluorescence staining of S100-β in a sagittal section of the facial nerve at 28 days after FNI.…”

Section: Discussionmentioning

confidence: 99%

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

et al. 2020

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Many factors are involved in the process of nerve regeneration. Understanding the mechanisms regarding how these factors promote an efficient remyelination is crucial to deciphering the molecular and cellular processes required to promote nerve repair. Schwann cells (SCs) play a central role in the process of peripheral nerve repair/regeneration. Using a model of facial nerve crush injury and repair, we identified Annexin A1 (ANXA1) as the extracellular trigger of SC proliferation and migration. ANXA1 activated formyl peptide receptor 2 (FPR2) receptors and the downstream adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK) signaling cascade, leading to SC proliferation and migration in vitro. SCs lacking FPR2 or AMPK displayed a defect in proliferation and migration. After facial nerve injury (FNI), ANXA1 promoted the proliferation of SCs and nerve regeneration in vivo. Collectively, these data identified the ANXA1/FPR2/AMPK axis as an important pathway in SC proliferation and migration. ANXA1‐induced remyelination and SC proliferation promotes FNI regeneration.

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Section: Discussionmentioning

confidence: 99%

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

et al. 2020

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“…As previously reported, exogenous IGF-1 sustains cell viability in cancer cell lines by stimulating mitochondrial biogenesis and BNIP3-induced mitophagy [35], and IGF-1 can also augment mitochondrial function and neuronal metabolism via AMPK [11]. However, no previous study has linked the IGF-1 and neuronal mitophagy in brain insults.…”

Section: Discussionmentioning

confidence: 91%

“…IGF-1 has shown to increase the mitophagy via activating AMPK signal [11]. We have shown mitophagy is impaired in the chronic stage of TBI [12,13], and accordingly we predict that this might be due to the lower IGF-1 status after TBI, as tau phosphorylation can disrupt the mitophagy [14].…”

Section: Introductionmentioning

confidence: 77%

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Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury

Ren¹,

Chen²,

Liang³

et al. 2020

Preprint

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Background Defective brain hormonal signaling and autophagy have been associated with neurodegeneration after brain insults, characterized by neuronal loss and cognitive dysfunction. However, less studies have link them in the context of brain injury. Insulin like growth factor-1 (IGF-1) is an important hormone that contributes to growth, cell proliferation and autophagy, also expressed in the brain. Methods We applied proteomics to investigate the role of astrocytic IGF-1 in TBI and related neuroprotective mechanisms. Results We found reduced plasma IGF-1 is correlated with cognition in TBI patients. Overexpression of astrocytic IGF-1 improves cognitive dysfunction in TBI mice and cocultured astrocytes prevent neuronal excitotoxicity with IGF-1 pathway dependent. At the molecular level, proteomics data show IGF-1 related NF-kB pathway transcriptionally regulates decapping mRNA2 (Dcp2) and miR-let-7, together with IGF-1R to orchestrate mitophagy in TBI. Finally, we demonstrate that TBI induces impaired mitophagy at the chronic stage and IGF-1 treatment could facilitate the mitophagy marker. Conclusion By showing that IGF-1 is an important mediator of the beneficial effect of neural-endocrine network in TBI models, our findings place IGF-1/IGF-1R as a potential target capable of non-coding RNAs and opposing mitophagy failure and cognition impairment in TBI.

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“…AMPKα2 is a key component in the regulation of insulin sensitivity [33,34] , and the lack of AMPKα2 can inhibit the resistibility of insulin in glucose uptake, which leading to abnormal glucose tolerance in vivo [35][36][37] . TBHQ can activate AMPKα2 and promote the autophagy of hepatocytes, thus exerting the effect of anti-fatty acid [17] .…”

Section: Discussionmentioning

confidence: 99%

Tertiary Butylhydroquinone Ameliorates Insulin Resistance and Liver Steatosis in Type 2 Diabetes Mellitus

Zhu

Liu

et al. 2020

Preprint

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Aims: This study aimed to evaluate the effects and mechanisms of tertiary butylhydroquinone (TBHQ) on insulin resistance (IR) and diabetic liver steatosis. Methods: Male ApoE-/- mice were received streptozocin (STZ) injection and a high-sugar-high-fat diet to form type 2 diabetes mellitus (T2DM). Then, the mice were given TBHQ for six weeks. Body weight, fasting blood-glucose (FBG), postprandial blood glucose (PBG), insulin and oral glucose tolerance test (OGTT) were detected on all the mice. Hematoxylin-eosin staining and western-blot were performed to detect the morphological structure and the target proteins expression in liver tissues. In vitro, HepG2 cells were induced by HClO and insulin to develop IR. Western-blot was used to evaluate the related proteins expression. Hoechst staining was conducted to measure cell apoptosis. Results: Mice that received STZ injection and a high-sugar-high-fat diet developed T2DM. TBHQ reduced blood glucose level, improved glucose tolerance, alleviated liver steatosis in diabetic mice. Moreover, TBHQ significantly increased AMPKα2, GLUT4 and GSK3β expression, up-regulated PI3K and AKT phosphorylation level in diabetic mice liver. Notably, TBHQ down-regulated HClO and insulin-induced cell IR and inhibited cell apoptosis via AMPKα2/PI3K/AKT pathway. Conclusion: TBHQ alleviated IR and liver steatosis in T2DM mice and the mechanism may relate to AMPKα2/PI3K/AKT pathway.

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Insulin-like growth factor-1 activates AMPK to augment mitochondrial function and correct neuronal metabolism in sensory neurons in type 1 diabetes

Cited by 53 publications

References 86 publications

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway

Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury

Tertiary Butylhydroquinone Ameliorates Insulin Resistance and Liver Steatosis in Type 2 Diabetes Mellitus

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