AT1 receptor downregulation: A mechanism for improving glucose homeostasis

World J Diabetes. 2023 Mar 15;14(3):170-178. doi: 10.4239/wjd.v14.i3.170.

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: AT1 receptor; Angiotensin II signaling pathway; High blood pressure; Insulin receptor; Insulin signaling pathway; Type 2 diabetes mellitus.

Publication types

  • Review