2019年1月
p62-mediated autophagy affects nutrition-dependent insulin receptor substrate 1 dynamics in 3T3-L1 preadipocytes.
Journal of diabetes investigation
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- 巻
- 10
- 号
- 1
- 開始ページ
- 32
- 終了ページ
- 42
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/jdi.12866
AIMS/INTRODUCTION: Previous studies have shown that an organism's nutritional status changes the protein levels of insulin receptor substrate 1 (IRS-1) in a tissue-specific manner. Although the mechanisms underlying the regulation of IRS-1 in the nutrient-rich conditions associated with diabetes and insulin resistance have been well studied, those under nutrient-poor conditions remain unknown. The aim of the present study was to investigate how IRS-1 protein levels change depending on the nutritional status of 3T3-L1 preadipocytes. MATERIALS AND METHODS: 3T3-L1 preadipocytes were treated with glucose-, amino acid- and serum-free medium for starvation. IRS-1 protein levels were detected by western blot. Autophagy activity was observed by western blot and fluorescence microscopy. The effect of autophagy and p62, an adaptor for selective autophagy, on IRS-1 protein levels under starvation conditions was examined by western blot and immunocytochemistry. RESULTS: We showed that the levels of IRS-1, but not those of insulin receptor and protein kinase B, decreased when starvation activated autophagy. The inhibition of autophagy by chloroquine or autophagy-related 7 (Atg7) ribonucleic acid interference counteracted the starvation-induced decrease of IRS-1. Additionally, Atg7 knockdown increased insulin-stimulated phosphorylation of protein kinase B under starvation conditions. Furthermore, p62 colocalized with IRS-1 under starvation conditions, and p62 knockdown counteracted the starvation-induced degradation of IRS-1. CONCLUSIONS: Autophagy through p62 plays an important role in regulating IRS-1 protein levels in response to nutritional deficiency. The present findings suggest that autophagy might function as energy depletion-sensing machinery that finely tunes insulin signal transduction.
- リンク情報
- ID情報
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- DOI : 10.1111/jdi.12866
- ISSN : 2040-1116
- PubMed ID : 29786968
- PubMed Central 記事ID : PMC6319485