Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway

Abstract

Our findings suggest a potential role of adiponectin/APPL1 signaling in mediating the effect of incretin in the prevention of atherosclerosis progression or plaque vulnerability in T2DM.

Incretin drugs effect on epigenetic machinery: New potential therapeutic implications in preventing vascular diabetic complications

“…13 Moreover, a study conducted on patients showed that incretin treatment, via adiponectin/APPL1 signaling pathway, prevents atherosclerosis progression or plaque vulnerability in type 2 diabetes patients. 14 More intriguing, recent studies demonstrated that exendin-4 (also known as exenatide), a GLP-1R agonist, regulates the expression of extracellular-superoxide dismutase (EC-SOD), in A549 cells, by reducing DNMTs activity with consequently DNA demethylation in the EC-SOD promoter region. 15 Furthermore, in animal model of type 2 diabetes, exendin-4 treatment in the new-born period reversed the aberrant epigenetic modifications at pancreatic and duodenal home box 1 (Pdx1) promoter in intrauterine growth restriction (IUGR) islets preventing the development of diabetes in adulthood.…”

Analysis of APPL1 Gene Polymorphisms in Patients with a Phenotype of Maturity Onset Diabetes of the Young

“…Although APPL1 is known to be an adaptor in multiple signaling pathways, phenotypic manifestations of its variants remain elusive. It is known that adiponectin has an antiatherosclerotic effect [ 36 ]. In atherosclerotic plaques of patients with T2DM, APPL1 is underexpressed relative to patients without diabetes [ 36 ].…”

Effect of sitagliptin on tissue characteristics of the carotid wall in patients with type 2 diabetes: a post hoc sub-analysis of the sitagliptin preventive study of intima-media thickness evaluation (SPIKE)

“…Interestingly, atherosclerotic plaques of T2DM patients showed lower levels of adiponectin and adaptor protein PH domain and leucine zipper containing 1 (APPL1), an adaptor protein that interact directly with adiponectin receptors, compared with non-diabetic patients. It was also shown that current incretin-users presented higher adiponectin and APPL1 content compared with never incretin users [ 37 ]. These findings suggest a potential role of adiponectin/APPL1 signaling mediating the beneficial effect of sitagliptin on the tissue characteristic of the carotid arterial wall.…”