澳大利亚悉尼大学David E. James团队揭示驱动胰岛素抵抗的组织和途径特异性的相互作用。这一研究成果于2022年1月11日在线发表在国际学术期刊《细胞—代谢》上。
Author: Marin E. Nelson, Sren Madsen, Kristen C. Cooke, Andreas M. Fritzen, Ida H. Thorius, Stewart W.C. Masson, Luke Carroll, Fiona C. Weiss, Marcus M. Seldin, Meg Potter, Samantha L. Hocking, Daniel J. Fazakerley, Amanda E. Brandon, Senthil Thillainadesan, Alistair M. Senior, Gregory J. Cooney, Jacqueline Stckli, David E. James
Abstract: Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolicdisease. To uncover pathways involved in insulin resistance, specifically in thesetissues, we leveraged the metabolic diversity of different dietary exposures and discreteinbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-environmentinteractions and was strongly correlated with hyperinsulinemia and decreased levelsof ten key glycolytic enzymes. Remarkably, there was no relationship between muscleand adipose tissue insulin action. Adipocyte size profoundly varied across strainsand diets, and this was strongly correlated with adipose tissue insulin resistance.The A/J strain, in particular, exhibited marked adipocyte insulin resistance and hypertrophydespite robust muscle insulin responsiveness, challenging the role of adipocyte hypertrophyper se in systemic insulin resistance. These data demonstrate that muscle and adiposetissue insulin resistance can occur independently and underscore the need for tissue-specificinterrogation to understand metabolic disease.