Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice
| Autor: | Junjie Yu, Jianmin Zhu, Yajie Guo, Fei Xiao, Ying Du, Kai Li, Feifan（郭非凡） Guo, Hongguang Sheng, Shanghai（陈上海） Chen, Jiali Deng |
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| Rok vydání: | 2014 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Blotting Western P70-S6 Kinase 1 Carbohydrate metabolism AMP-Activated Protein Kinases Ribosomal Protein S6 Kinases 90-kDa Cell Line Mice Endocrinology Insulin resistance AMP-activated protein kinase Valine Internal medicine medicine Animals Humans Isoleucine biology Reverse Transcriptase Polymerase Chain Reaction TOR Serine-Threonine Kinases Gluconeogenesis Ribosomal Protein S6 Kinases 70-kDa Hep G2 Cells medicine.disease Mice Inbred C57BL Insulin receptor Biochemistry biology.protein Glucose-6-Phosphatase Hepatocytes Leucine Insulin Resistance Amino Acids Branched-Chain Signal Transduction |
| Zdroj: | Metabolism: clinical and experimental. 63(6) |
| ISSN: | 1532-8600 |
| Popis: | Objective We recently discovered that leucine deprivation increases hepatic insulin sensitivity via general control nondepressible (GCN) 2/mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways. The goal of the present study was to investigate whether the above effects were leucine specific or were also induced by deficiency of other branched chain amino acids including valine and isoleucine. Methods Following depletion of BCAAs, changes in metabolic parameters and the expression of genes and proteins involved in regulation of insulin sensitivity and glucose metabolism were analyzed in mice and cell lines including human HepG2 cells, primary mouse hepatocytes and a mouse myoblast cell line C2C12. Results Valine or isoleucine deprivation for 7 days has similar effect on improving insulin sensitivity as leucine, in wild type and insulin-resistant mice models. These effects are possibly mediated by decreased mTOR/S6K1 and increased AMPK signaling pathways, in a GCN2-dependent manner. Similar observations were obtained in in vitro studies. In contrast to leucine withdrawal, valine or isoleucine deprivation for 7 days significantly decreased fed blood glucose levels, possibly due to reduced expression of a key gluconeogenesis gene, glucose-6-phosphatase. Finally, insulin sensitivity was rapidly improved in mice 1 day following maintenance on a diet deficient for any individual BCAAs. Conclusions Our results show that while improvement on insulin sensitivity is a general feature of BCAAs depletion, individual BCAAs have specific effects on metabolic pathways, including those that regulate glucose level. These observations provide a conceptual framework for delineating the molecular mechanisms that underlie amino acid regulation of insulin sensitivity. |
| Databáze: | OpenAIRE |
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