Nemati Marzieh, Siri Morvarid, Ebrahimi Bahareh, Hosseinzadeh Zahra, Molayem Mina, Mokarram Pooneh, Dastghaib Sanaz
Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
J Diabetes Metab Disord. 2024 Jun 12;23(2):1601-1612. doi: 10.1007/s40200-024-01451-1. eCollection 2024 Dec.
The Endoplasmic reticulum (ER) organelle is necessary for protein folding and, in this regard, has a determined capacity. Increased protein synthesis beyond endoplasmic reticulum capacity, leads to ER dyshomeostasis, unfolded proteins accumulation, ER stress, and unfolded protein response (UPR) induction which mediating by three transmembrane sensor proteins. Various studies have shown that in diabetes, greater demand for insulin production is one of the causes of UPR induction giving rise both ameliorative and destructive effects through modulation activity of different branches. Our purpose is to investigate precise role of UPR on diabetes management.
Inclusion criteria were English language and full text publications. Diseases other than diabetes and mechanisms other than UPR were excluded. Search was done in PubMed, web of science (WOS) and Scopus using keywords.
After assessing bias, total of 22,364 articles were initially identified. Duplication (1593) was deleted using hand- screening, 20,771 papers met all inclusion criteria and selected. Both review and unrelated articles were excluded. Finally, 36 articles assessed for the precise role of the UPR on diabetes management. The most of studies (29) showed improving effects of UPR, (17 studies) investigated activity of only one arm, and protein kinase RNA like endoplasmic reticulum kinase (PERK) was the most investigated (31) arm. Different findings might be explained by different endoplasmic reticulum stress induction strategies, treatment duration, and varied investigations in these studies. We summarize the role of UPR on diabetes management, but despite promising and ameliorating results of this review, further studies are needed to clarify the helpfulness in clinical management of diabetes.
内质网细胞器对于蛋白质折叠是必需的，在这方面，它具有一定的容量。当蛋白质合成增加超过内质网容量时，会导致内质网动态平衡失调、未折叠蛋白积累、内质网应激以及由三种跨膜传感器蛋白介导的未折叠蛋白反应（UPR）的诱导。各种研究表明，在糖尿病中，对胰岛素产生的更高需求是UPR诱导的原因之一，通过调节不同分支的活性产生改善和破坏两种作用。我们的目的是研究UPR在糖尿病管理中的精确作用。
纳入标准为英文全文出版物。排除糖尿病以外的疾病和UPR以外的机制。使用关键词在PubMed、科学网（WOS）和Scopus中进行检索。
在评估偏倚后，最初共识别出22364篇文章。通过手工筛选删除重复项（1593篇），20771篇论文符合所有纳入标准并被选中。综述和不相关的文章均被排除。最后，对36篇文章评估了UPR在糖尿病管理中的精确作用。大多数研究（共29项）显示了UPR的改善作用，（17项研究）仅研究了一条途径的活性，而蛋白激酶RNA样内质网激酶（PERK）是研究最多的（31项）途径。这些研究中不同的结果可能由不同的内质网应激诱导策略、治疗持续时间以及不同的研究方法来解释。我们总结了UPR在糖尿病管理中的作用，但尽管本综述有前景且结果改善，但仍需要进一步研究以阐明其在糖尿病临床管理中的有效性。
