AdipoRon, adiponectin receptor agonist, improves vascular function in the mesenteric arteries of type 2 diabetic mice

Abstract

BackgroundAdiponectin is one of the most abundant adipokines secreted from adipose tissue. An orally active synthetic adiponectin receptor agonist, adipoRon has been suggested to ameliorate insulin resistance, myocardial apoptosis, and pancreatic tumor. It has been reported that adiponectin directly induces vascular relaxation however, the chronic effect of adipoRon in the vascular dysfunction in type 2 diabetes has not been studied yet. Thus, in this study, we examined whether adipoRon improves vascular function in type 2 diabetes and what mechanism is involved.MethodsTen to 12‐week old male type 2 diabetic (db−/db−) mice were treated with adiponectin receptor agonist (adipoRon, 10 mg/kg/everyday, by oral gavage) for 2 weeks. Isolated mesenteric arteries were mounted in the arteriography and arterial diameter was measured. And western blot analysis was assessed.ResultsPressure‐induced myogenic response was significantly increased, whereas endothelium‐dependent relaxation was significantly reduced in the mesenteric arteries from type 2 diabetic mice. Interestingly, treatment of adipoRon normalized potentiated myogenic response. However, endothelium‐dependent relaxation was not affected by treatment of adipoRon. The expression levels of adiponectin receptor 1, 2 and adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1, 2 (APPL 1, 2) were increased in the mesenteric arteries from Type 2 diabetic mice and treatment of adipoRon did not affect them. Interestingly, adipoRon treatment increased the phosphorylation level of AMP‐activated protein kinase (AMPK) and decreased phosphorylation of myosin phosphatase target subunit 1 (MYPT1) in the type 2 diabetic mice while there was no change in the level of eNOS phosphorylation.ConclusionThe treatment of adipoRon improves vascular function in the mesenteric arteries from type 2 diabetic mice through endothelium‐independent mechanism. We suggest that myosin light chain phosphatase (MLCP) activation through reduced phosphorylation of MYPT1 might be the dominant mechanism in the adipoRon‐induced vascular effect.Support or Funding InformationThis work was supported by the Basic Science Research Program of the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (NRF‐2018R1D1A1B07041820).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.