<p>Metformin Decreases Insulin Resistance in Type 1 Diabetes Through Regulating p53 and RAP2A in vitro and in vivo</p>
Authors: Gao-Fei Ren
Yu-Shan Yan
Xiao-Jun Ma
Li-Li Xiao
Peng-Fei Jiao
Journal: Drug Design Development and Therapy (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: RAP2A; insulin resistance; metformin; p53; type 1 diabetes.
Affiliations: Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, People's Republic of China., Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, People's Republic of China., Department of Respiratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, People's Republic of China.

Abstract:  Purpose: Patients with type 1 diabetes (T1D) are associated with a high risk of multiple complications, so the development of T1D treatment is urgently needed. This study was set out to explore the molecular mechanism of metformin in the treatment of T1D insulin resistance. Patients and methods: Subcutaneous adipose tissues were collected from 68 T1D patients and 51 healthy controls. Insulin resistance model rats and cells were constructed and treated with metformin respectively. Western blot was used to detect p53 and RAP2A protein levels, and qPCR was utilized to measure p53 and RAP2A mRNA levels. SiRNA and RAP2A siRNA vectors were constructed to observe their effects on insulin resistance model cells. Results: In T1D, p53 was up-regulated, while RAP2A was down-regulated. Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A. P53 induced insulin resistance and inflammatory response by inhibiting RAP2A and promoted apoptosis. Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance. 

Retracted: Yes

PubPeer comments:
 The Western blots throughout this paper have backgrounds with unexpectedly shared features. *Some* are highlighted in Figure 2 below as an example (there are others). Can the authors please explain? I would like to note for readers that the corresponding email address bears no resemblance to the name of the corresponding author. *** ![file] , 
 Retracted [8 June 2021] . --------------------------------------------- The Editor-in-chief and Publisher of Drug Design, Development and Therapy wish to retract the published article. The journal was notified of alleged image manipulation relating to the western blot images presented in the article. Specifically: - The background of the western blot images shown in Figure 2C panels p53 and RAP2A appear to show repeated features. - The background of the western blot image shown in Figure 2C panel u03b2-actin appears to show repeated features. - The background of the western blot images shown in Figure 3A panels IR3K, p-PI3K and p-Akt appear to show repeated features. - The background of the western blot image shown in Figure 3A panel u03b2-actin appears to show repeated features. - The background of the western blot images shown in Figure 3B panels IR3K, p-PI3K and p-Akt appear to show repeated features. - The background of the western blot images shown in Figure 4A panels Caspase 3, Caspase 9, Bax and Bcl2 appear to show repeated features. - The background of the western blot images shown in Figure 4B panels Caspase 3, Caspase 9, Bax and Bcl2 appear to show repeated features. - The background of the western blot images shown in Figure 5A panels NF-u03baB p65, TNF-u03b1, IL-8 and IL-6 appear to show repeated features. - The background of the western blot images shown in Figure 5A panel u03b2-actin appears to show repeated features. - The background of the western blot images shown in Figure 5B panels NF-u03baB p65, TNF-u03b1, IL-8 and IL-6 appear to show repeated features. Despite multiple attempts the authors were unable to be contacted and could not provide an explanation for the alleged duplication. The decision was made to retract the paper. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,