Alexandria V Harrison, Felipe Ramos Lorenzo, Donald A McClain
{"title":"Iron and the Pathophysiology of Diabetes.","authors":"Alexandria V Harrison, Felipe Ramos Lorenzo, Donald A McClain","doi":"10.1146/annurev-physiol-022522-102832","DOIUrl":null,"url":null,"abstract":"<p><p>High iron is a risk factor for type 2 diabetes mellitus (T2DM) and affects most of its cardinal features: decreased insulin secretion, insulin resistance, and increased hepatic gluconeogenesis. This is true across the normal range of tissue iron levels and in pathologic iron overload. Because of iron's central role in metabolic processes (e.g., fuel oxidation) and metabolic regulation (e.g., hypoxia sensing), iron levels participate in determining metabolic rates, gluconeogenesis, fuel choice, insulin action, and adipocyte phenotype. The risk of diabetes related to iron is evident in most or all tissues that determine diabetes phenotypes, with the adipocyte, beta cell, and liver playing central roles. Molecular mechanisms for these effects are diverse, although there may be integrative pathways at play. Elucidating these pathways has implications not only for diabetes prevention and treatment, but also for the pathogenesis of other diseases that are, like T2DM, associated with aging, nutrition, and iron.</p>","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":15.7000,"publicationDate":"2023-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161568/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-physiol-022522-102832","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
High iron is a risk factor for type 2 diabetes mellitus (T2DM) and affects most of its cardinal features: decreased insulin secretion, insulin resistance, and increased hepatic gluconeogenesis. This is true across the normal range of tissue iron levels and in pathologic iron overload. Because of iron's central role in metabolic processes (e.g., fuel oxidation) and metabolic regulation (e.g., hypoxia sensing), iron levels participate in determining metabolic rates, gluconeogenesis, fuel choice, insulin action, and adipocyte phenotype. The risk of diabetes related to iron is evident in most or all tissues that determine diabetes phenotypes, with the adipocyte, beta cell, and liver playing central roles. Molecular mechanisms for these effects are diverse, although there may be integrative pathways at play. Elucidating these pathways has implications not only for diabetes prevention and treatment, but also for the pathogenesis of other diseases that are, like T2DM, associated with aging, nutrition, and iron.
期刊介绍:
Since 1939, the Annual Review of Physiology has been highlighting significant developments in animal physiology. The journal covers diverse areas, including cardiovascular physiology, cell physiology, ecological, evolutionary, and comparative physiology, endocrinology, gastrointestinal physiology, neurophysiology, renal and electrolyte physiology, respiratory physiology, and special topics.