AKT2 regulates development and metabolic homeostasis via AMPK-depedent pathway in skeletal muscle
| Autor: | Miao Chen, Yaoting Li, Fangrong Yan, Junmei Ye, Xingyu Gao, Nan Jiang, Kaidi Zhang, Shuya Gao, Yubin Zhang, Yue Peng, Xiaohong Bian, Daniel Sanchis, Caoyu Ji, Caiping Chen, Qingchen Yang, Zhe Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mef2 Aging Sarcopenia medicine.medical_specialty Glucose uptake medicine.medical_treatment AMP-Activated Protein Kinases 030204 cardiovascular system & hematology Carbohydrate metabolism Models Biological Cell Line 03 medical and health sciences 0302 clinical medicine Insulin resistance Loss of Function Mutation Internal medicine medicine Animals Homeostasis Gene Regulatory Networks Muscle Skeletal Mice Knockout Organelle Biogenesis MEF2 Transcription Factors Chemistry Insulin AMPK Skeletal muscle Organ Size General Medicine Ribonucleotides Aminoimidazole Carboxamide medicine.disease Mice Inbred C57BL Glucose 030104 developmental biology Endocrinology medicine.anatomical_structure Mitochondrial biogenesis Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Clinical Science. 134:2381-2398 |
| ISSN: | 1470-8736 0143-5221 |
| Popis: | Skeletal muscle is responsible for the majority of glucose disposal in the body. Insulin resistance in the skeletal muscle accounts for 85–90% of the impairment of total glucose disposal in patients with type 2 diabetes (T2D). However, the mechanism remains controversial. The present study aims to investigate whether AKT2 deficiency causes deficits in skeletal muscle development and metabolism, we analyzed the expression of molecules related to skeletal muscle development, glucose uptake and metabolism in mice of 3- and 8-months old. We found that AMP-activated protein kinase (AMPK) phosphorylation and myocyte enhancer factor 2 (MEF2) A (MEF2A) expression were down-regulated in AKT2 knockout (KO) mice, which can be inverted by AMPK activation. We also observed reduced mitochondrial DNA (mtDNA) abundance and reduced expression of genes involved in mitochondrial biogenesis in the skeletal muscle of AKT2 KO mice, which was prevented by AMPK activation. Moreover, AKT2 KO mice exhibited impaired AMPK signaling in response to insulin stimulation compared with WT mice. Our study establishes a new and important function of AKT2 in regulating skeletal muscle development and glucose metabolism via AMPK-dependent signaling. |
| Databáze: | OpenAIRE |
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