Jelena Kolic, WenQing Grace Sun, Haoning Howard Cen, Jessica D. Ewald, Jason C. Rogalski, Shugo Sasaki, Han Sun, Varsha Rajesh, Yi Han Xia, Renata Moravcova, Søs Skovsø, Aliya F. Spigelman, Jocelyn E. Manning Fox, James Lyon, Leanne Beet, Jianguo Xia, Francis C. Lynn, Anna L. Gloyn, Leonard J. Foster, Patrick E. MacDonald, James D. Johnson
{"title":"Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease","authors":"Jelena Kolic, WenQing Grace Sun, Haoning Howard Cen, Jessica D. Ewald, Jason C. Rogalski, Shugo Sasaki, Han Sun, Varsha Rajesh, Yi Han Xia, Renata Moravcova, Søs Skovsø, Aliya F. Spigelman, Jocelyn E. Manning Fox, James Lyon, Leanne Beet, Jianguo Xia, Francis C. Lynn, Anna L. Gloyn, Leonard J. Foster, Patrick E. MacDonald, James D. Johnson","doi":"10.1016/j.cmet.2024.06.001","DOIUrl":null,"url":null,"abstract":"<p>Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors’ islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors’ islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein—potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"19 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2024.06.001","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors’ islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors’ islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein—potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.