Improvement of CGRP on vascular endothelial cells insulin resistance via activation of cAMP/PPARγ/eNOS pathway

doi:10.12092/j.issn.1009-2501.2019.06.003

Abstract

Abstract:

AIM: To explore the protective effect and the mechanism of calcitonin gene-relatedpeptide (CGRP) on the insulin-resisted human umbilical vein endothelial cells (irHUVECs). METHODS: The irHUVECs was established using human umbilical veinendothelial cells (HUVECs), gucose oxidase (GOP-POD) method and anthrone-sulfuric acid method were employed to detect glucose consumption ability and glycogen synthesis ability, respectively. RT-PCR and Western blot were used to detect the mRNA and protein expressions of peroxisome proliferator-activated receptor gamma (PPARγ) and endothelial nitric oxide synthase (eNOS), respectively. RESULTS:The irHUVECs was successfully established when the HUVECs were treated with 33.3 mmol/L high glucose and 5 μmol/L insulin. Compared to the normal group of endothelial cells, the features of irHUVECs were a larger volume, fuzzy boundary and abnormal morphology, when cells induced were incubated with high glucose and high insulin in 24 h and 48 h, respectively, the glucose consumption was reduced by 20% and 31%, and the glycogen synthesis was reduced by 55% and 64%, meanwhile, the expressions of PPARγ and eNOS were decreased. Treatment of CGRP significantly increased about 20% glucose consumption and about 70% glycogen synthesis, and increased the expressions of PPARγ and eNOS, SQ22536 (cAMP inhibitor) can decreased the expressions of PPARγ and eNOS. CONCLUSION: CGRP could improve the endothelial cell insulin resistance, the mechanism may be related to up-regulated cAMP, and the increased expressions of PPARγ and eNOS.

Key words: calcitonin gene related peptide, human umbilical vein endothelial cells, insulin resistance, PPARγ, eNOS, cAMP

CLC Number:

R587.1
R966

QUAN Haiyan, LIU Yuhuan, YANG Li, YANG Fang, QIN Xuping. Improvement of CGRP on vascular endothelial cells insulin resistance via activation of cAMP/PPARγ/eNOS pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(6): 615-622.

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