We have located links that may give you full text access.
GLP-1 modulates insulin-induced relaxation response through β-arrestin2 regulation in diabetic mice aortas.
Acta Physiologica 2020 October 25
AIMS: Diabetes impairs insulin-induced endothelium-dependent relaxation by reducing nitric oxide (NO) production. GLP-1, an incretin hormone, has been shown to prevent the development of endothelial dysfunction. In this study, we hypothesized that GLP-1 would improve the impaired insulin-induced relaxation response in diabetic mice. We also examined the underlying mechanisms.
METHODS: Using aortic rings from ob/ob mice, an animal model of obesity and type 2 diabetes, and lean mice, vascular relaxation responses and protein expressions were evaluated using insulin, GLP-1, and pathway-specific inhibitors to elucidate the mechanisms of response. In parallel experiments, β-arrestin2 siRNA-transfected aortas were treated with GLP-1 to evaluate its effects on aortic response pathways.
RESULTS: When compared to that of untreated ob/ob aortas, GLP-1 increased insulin-induced vasorelaxation and NO production. AMPK inhibition did not alter this vasorelaxation in both GLP-1-treated lean and ob/ob aortas, while Akt inhibition reduced vasorelaxation in both groups, and co-treatment with GLP-1 and insulin caused Akt/eNOS activation. Additionally, GLP-1 decreased GRK2 activity and enhanced β-arrestin2 translocation from the cytosol to membrane in ob/ob aortas. β-Arrestin2 siRNA decreased insulin-induced relaxation both in lean aortas and GLP-1-treated ob/ob aortas.
CONCLUSIONS: We demonstrated that insulin-induced relaxation is dependent on β-arrestin2 translocation and Akt activation via GLP-1-stimulated GRK2 inactivation in ob/ob aortas. We showed a novel cross-talk between GLP-1-responsive β-arrestin2 and insulin signaling in diabetic aortas.
METHODS: Using aortic rings from ob/ob mice, an animal model of obesity and type 2 diabetes, and lean mice, vascular relaxation responses and protein expressions were evaluated using insulin, GLP-1, and pathway-specific inhibitors to elucidate the mechanisms of response. In parallel experiments, β-arrestin2 siRNA-transfected aortas were treated with GLP-1 to evaluate its effects on aortic response pathways.
RESULTS: When compared to that of untreated ob/ob aortas, GLP-1 increased insulin-induced vasorelaxation and NO production. AMPK inhibition did not alter this vasorelaxation in both GLP-1-treated lean and ob/ob aortas, while Akt inhibition reduced vasorelaxation in both groups, and co-treatment with GLP-1 and insulin caused Akt/eNOS activation. Additionally, GLP-1 decreased GRK2 activity and enhanced β-arrestin2 translocation from the cytosol to membrane in ob/ob aortas. β-Arrestin2 siRNA decreased insulin-induced relaxation both in lean aortas and GLP-1-treated ob/ob aortas.
CONCLUSIONS: We demonstrated that insulin-induced relaxation is dependent on β-arrestin2 translocation and Akt activation via GLP-1-stimulated GRK2 inactivation in ob/ob aortas. We showed a novel cross-talk between GLP-1-responsive β-arrestin2 and insulin signaling in diabetic aortas.
Full text links
Related Resources
Trending Papers
Systemic lupus erythematosus.Lancet 2024 April 18
Should renin-angiotensin system inhibitors be held prior to major surgery?British Journal of Anaesthesia 2024 May
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.International Journal of Molecular Sciences 2024 April 13
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app