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World J Diabetes. Mar 15, 2023; 14(3): 170-178
Published online Mar 15, 2023. doi: 10.4239/wjd.v14.i3.170
AT1 receptor downregulation: A mechanism for improving glucose homeostasis
Diana L Lopez, Oscar E Casillas, Hiram J Jaramillo, Tatiana Romero-Garcia, J. Gustavo Vazquez-Jimenez
Diana L Lopez, Hiram J Jaramillo, Department of Internal Medicine, General Hospital of Mexicali, Mexicali 21000, Baja California, Mexico
Oscar E Casillas, J. Gustavo Vazquez-Jimenez, Faculty of Medicine, Autonomous University of Baja California, Mexicali 21000, Baja California, Mexico
Tatiana Romero-Garcia, Faculty of Sports, Autonomous University of Baja California, Mexicali 21289, Baja California, Mexico
Author contributions: Vazquez-Jimenez JG designed the research study; Lopez DL and Jaramillo HJ performed the research; Casillas OE, Romero-Garcia T, and Vazquez-Jimenez JG analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: J. Gustavo Vazquez-Jimenez, MD, PhD, Doctor, Research Scientist, Research Scientist, Faculty of Medicine, Autonomous University of Baja California, Centro Cívico, Mexicali 21000, Baja California, Mexico. gustavo.vazquez@uabc.edu.mx
Received: November 15, 2022
Peer-review started: November 15, 2022
First decision: December 26, 2022
Revised: January 13, 2023
Accepted: February 22, 2023
Article in press: February 22, 2023
Published online: March 15, 2023
Abstract

There is a pathophysiological correlation between arterial hypertension and diabetes mellitus, established since the pre-diabetic state in the entity known as insulin resistance. It is known that high concentrations of angiotensin-II enable chronic activation of the AT1 receptor, promoting sustained vasoconstriction and the consequent development of high blood pressure. Furthermore, the chronic activation of the AT1 receptor has been associated with the development of insulin resistance. From a molecular outlook, the AT1 receptor signaling pathway can activate the JNK kinase. Once activated, this kinase can block the insulin signaling pathway, favoring the resistance to this hormone. In accordance with the previously mentioned mechanisms, the negative regulation of the AT1 receptor could have beneficial effects in treating metabolic syndrome and type 2 diabetes mellitus. This review explains the clinical correlation of the metabolic response that diabetic patients present when receiving negatively regulatory drugs of the AT1 receptor.

Keywords: Type 2 diabetes mellitus, High blood pressure, Insulin receptor, Insulin signaling pathway, AT1 receptor, Angiotensin II signaling pathway

Core Tip: Type 2 diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, whose chronic lack of control is associated with the development of several manifestations that can incapacitate the patient. Recently, it has been described that the prescription of antihypertensive drugs in the presence of proteinuria in diabetic patients can prevent kidney failure, and notably, antihypertensive drugs can also be coadjuvant to improve glucose homeostasis. In this review, we disclose the pathophysiological mechanism in which hypertension is related to the development of insulin resistance, contrasting it with the results obtained during clinical practice, giving a new approach to the use of antihypertensive drugs that beyond avoiding kidney damage, are coadjuvant in the treatment of T2DM.