AKT2 regulates development and metabolic homeostasis via AMPK-depedent pathway in skeletal muscle.

Abstract

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.

• Authors: Miao Chen, Caoyu Ji, Qingchen Yang, Shuya Gao, Yue Peng, Zhe Li, Xingyu Gao, Yaoting Li, Nan Jiang, Yubin Zhang, Xiaohong Bian, Caiping Chen, Kaidi Zhang, Daniel Sanchis, Fangrong Yan, Junmei Ye
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 134 Issue 17 Pg. 2381-2398 (09 18 2020) ISSN: 1470-8736 [Electronic] England
• PMID: 32880392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Chemical References

• MEF2 Transcription Factors
• Ribonucleotides
• Aminoimidazole Carboxamide
• Akt2 protein, mouse
• Proto-Oncogene Proteins c-akt
• AMP-Activated Protein Kinases
• AICA ribonucleotide
• Glucose

Topics

• AMP-Activated Protein Kinases (metabolism)
• Aging (metabolism)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology)
• Animals
• Cell Line
• Gene Regulatory Networks (drug effects)
• Glucose (metabolism)
• Homeostasis (drug effects)
• Loss of Function Mutation
• MEF2 Transcription Factors (metabolism)
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Biological
• Muscle, Skeletal (drug effects, enzymology, metabolism, ultrastructure)
• Organ Size (drug effects)
• Organelle Biogenesis
• Proto-Oncogene Proteins c-akt (deficiency, metabolism)
• Ribonucleotides (pharmacology)
• Sarcopenia (pathology)
• Signal Transduction (drug effects)