AGEs-Induced and Endoplasmic Reticulum Stress/Inflammation-Mediated Regulation of GLUT4 Expression and Atherogenesis in Diabetes Mellitus

In recent decades, complex and exquisite pathways involved in the endoplasmic reticulum (ER) and inflammatory stress responses have been demonstrated to participate in the development and progression of numerous diseases, among them diabetes mellitus (DM). In those pathways, several players participate in both, reflecting a complicated interplay between ER and inflammatory stress. In DM, ER and inflammatory stress are involved in both the pathogenesis of the loss of glycemic control and the development of degenerative complications. Furthermore, hyperglycemia increases the generation of advanced glycation end products (AGEs), which in turn refeed ER and inflammatory stress, contributing to worsening glycemic homeostasis and to accelerating the development of DM complications. In this review, we present the current knowledge regarding AGEs-induced and ER/inflammation-mediated regulation of the expression of GLUT4 (solute carrier family 2, facilitated glucose transporter member 4), as a marker of glycemic homeostasis and of cardiovascular disease (CVD) development/progression, as a leading cause of morbidity and mortality in DM.

Automated summary

In recent years, research has shown that the endoplasmic reticulum (ER) and inflammatory stress play important roles in the development and progression of diabetes mellitus and its complications. The generation of advanced glycation end products (AGEs) due to hyperglycemia further exacerbates ER and inflammatory stress, leading to destabilization of glycemic control and accelerated development of complications.