Elevated expression of urotensin II and its receptor in skeletal muscle of diabetic mouse

Wang, Hongxia; Zeng, Xiang Jun; Liu, Yue; Wang, Jue; Lu, Lan; Hao, Gang; Zhang, Li Ke; Tang, Chao

doi:10.1016/j.regpep.2009.01.004

Cited by 16 publications

(13 citation statements)

References 38 publications

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“…52 UII serum level and UII binding, as well as UT protein and mRNA expression, are all significantly enhanced in the skeletal muscle of 2DM mice. 53 Here, we demonstrated that UII deletion significantly reduced serum insulin and glucose, and improved glucose and insulin tolerance. Furthermore, the use of SB657510A significantly improved glucose tolerance in apoE KO mice.…”

Section: Discussionmentioning

confidence: 67%

Genetic and Pharmacological Manipulation of Urotensin II Ameliorate the Metabolic and Atherosclerosis Sequalae in Mice

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Genest

Barrette

et al. 2012

ATVB

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Objective-Urotensin II (UII) is a potent vasoactive peptide that binds to the urotensin receptor-coupled receptor-14 (known as UT) and exerts a wide range of actions in humans and experimental animals. We tested the hypothesis that UII gene deletion or UT blockade ameliorate experimental atherosclerosis. Methods and Results-We observed a significant reduction in weight gain, visceral fat, blood pressure, circulating plasma lipids, and proatherogenic cytokines and improvement of glucose tolerance in UII knockout mice compared with wild type (P<0.05). Deletion of UII after an apolipoprotein E knockout resulted in a significant reduction in serum cytokines, adipokines, and aortic atherosclerosis compared with apolipoprotein E knockout mice. Similarly, treatment of apolipoprotein E knockout mice fed on high-fat diet with the UT antagonist SB657510A reduced weight gain, visceral fat, and hyperlipidemia and improved glucose tolerance (P<0.05) and attenuated the initiation and progression of atherosclerosis. The UT antagonist also decreased aortic extracellular signal-regulated kinase 1/2 phosphorylation and oxidant formation and serum level of cytokines (P<0.05). Conclusion-These

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Section: Discussionmentioning

confidence: 67%

Genetic and Pharmacological Manipulation of Urotensin II Ameliorate the Metabolic and Atherosclerosis Sequalae in Mice

You

Genest

Barrette

et al. 2012

ATVB

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“…UII is thought to play a role in atherosclerosis and may be particularly relevant in the diabetic setting, where plasma UII levels are elevated [21][22][23]. This is the first study to specifically investigate the role of UII and the UT in experimental and clinical diabetes-associated atherosclerosis.…”

Section: Discussionmentioning

confidence: 96%

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

et al. 2013

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Aims/hypothesis The small, highly conserved vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis. However, its effects in diabetes-associated atherosclerosis have not been assessed. Methods Endothelial cells were grown in normal-and highglucose (5 and 25 mmol/l) media with and without UII (10 −8 mol/l) and/or the UII receptor antagonist, SB-657510 (10 −8 mol/l). Apoe knockout (KO) mice with or without streptozotocin-induced diabetes were treated with or without SB-657510 (30 mgkg −1 day −1 ; n=20 per group) and followed for 20 weeks. Carotid endarterectomy specimens from diabetic and non-diabetic humans were also evaluated. Results In high (but not normal) glucose medium, UII significantly increased CCL2 (encodes macrophage chemoattractant protein 1 [MCP-1]) gene expression (human aortic endothelial cells) and increased monocyte adhesion (HUVECs). UII receptor antagonism in diabetic Apoe KO mice significantly attenuated diabetes-associated atherosclerosis and aortic staining for MCP-1, F4/80 (macrophage marker), cyclooxygenase-2, nitrotyrosine and UII. UII staining was significantly increased in carotid endarterectomies from diabetic compared with non-diabetic individuals, as was staining for MCP-1. Conclusions/interpretation This is the first report to demonstrate that UII is increased in diabetes-associated atherosclerosis in humans and rodents. Diabetes-associated plaque development was attenuated by UII receptor antagonism in the experimental setting. Thus UII may represent a novel therapeutic target in the treatment of diabetes-associated atherosclerosis.

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“…The Control group was incubated with fresh FCS free DMEM for 24h. The UII group was treated with UII (100 nmol/L) for 24h [8]. The UII+Apo group was treated with apocynin (200 µmol/L) for 30min, and then incubated with UII for 24h.…”

Section: Methodsmentioning

confidence: 99%

“…Besides its important role in the cardiovascular system, UII also participates in metabolic regulation and plays a significant role in diabetes and its complications [6,7]. Our previous studies demonstrated that the UII/UT system is up-regulated in the skeletal muscle of mice with type II diabetes mellitus (T2DM), and UII inhibited insulin-stimulated 2-DG uptake in skeletal muscle [8]. We speculated that skeletal muscle-derived UII might be involved as an autocrine/paracrine factor in the pathogenesis of skeletal muscle insulin resistance (IR), although the mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Urotensin II Inhibits Skeletal Muscle Glucose Transport Signaling Pathways via the NADPH Oxidase Pathway

Wang

Yang

et al. 2013

PLoS ONE

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Our previous studies have demonstrated that the urotensin (UII) and its receptor are up-regulated in the skeletal muscle of mice with type II diabetes mellitus (T2DM), but the significance of UII in skeletal muscle insulin resistance remains unknown. The purpose of this study was to investigate the effect of UII on NADPH oxidase and glucose transport signaling pathways in the skeletal muscle of mice with T2DM and in C2C12 mouse myotube cells. KK/upj-AY/J mice (KK) mice were divided into the following groups: KK group, with saline treatment for 2 weeks; KK+ urantide group, with daily 30 µg/kg body weight injections over the same time period of urantide, a potent urotensin II antagonist peptide; Non-diabetic C57BL/6J mice were used as normal controls. After urantide treatment, mice were subjected to an intraperitoneal glucose tolerance test, in addition to measurements of the levels of ROS, NADPH oxidase and the phosphorylated AKT, PKC and ERK. C2C12 cells were incubated with serum-free DMEM for 24 hours before conducting the experiments, and then administrated with 100 nM UII for 2 hours or 24 hours. Urantide treatment improved glucose tolerance, decreased the translocation of the NADPH subunits p40-phox and p47-phox, and increased levels of the phosphorylated PKC, AKT and ERK. In contrast, UII treatment increased ROS production and p47-phox and p67-phox translocation, and decreased the phosphorylated AKT, ERK1/2 and p38MAPK; Apocynin abrogated this effect. In conclusion, UII increased ROS production by NADPH oxidase, leading to the inhibition of signaling pathways involving glucose transport, such as AKT/PKC/ERK. Our data imply a role for UII at the molecular level in glucose homeostasis, and possibly in skeletal muscle insulin resistance in T2DM.

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Elevated expression of urotensin II and its receptor in skeletal muscle of diabetic mouse

Cited by 16 publications

References 38 publications

Genetic and Pharmacological Manipulation of Urotensin II Ameliorate the Metabolic and Atherosclerosis Sequalae in Mice

Genetic and Pharmacological Manipulation of Urotensin II Ameliorate the Metabolic and Atherosclerosis Sequalae in Mice

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

Urotensin II Inhibits Skeletal Muscle Glucose Transport Signaling Pathways via the NADPH Oxidase Pathway

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