Importance of unfolded protein response modulation on diabetes management: a systematic review.

PURPOSE

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.

METHODS

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.

RESULTS

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.