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Université de Fribourg

Arginase-II promotes tumor necrosis Factor-α release from pancreatic acinar cells causing β-cell apoptosis in aging

Xiong, Yuyan ; Yepuri, Gautham ; Necetin, Sevil ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: Diabetes, 2017, vol. 66, no. 6, p. 1636–1649

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L-arginine- ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II−/−) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin...

Université de Fribourg

Genetic targeting of arginase-ii in mouse prevents renal oxidative stress and inflammation in diet-induced obesity

Huang, Ji ; Rajapakse, Angana ; Xiong, Yuyan ; Montani, Jean-Pierre ; Verrey, François ; Ming, Xiu-Fen ; Yang, Zhihong

In: Frontiers in Physiology, 2016, vol. 7, p. -

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L- arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase- II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and...

Université de Fribourg

"En Face" detection of nitric oxide and superoxide in endothelial layer of intact arteries

Yu, Yi ; Xiong, Yuyan ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Journal of Visualized Experiments, 2016, no. 108, p. -

Endothelium-derived nitric oxide (NO) produced from endothelial NO-synthase (eNOS) is one of the most important vasoprotective molecules in cardiovascular physiology. Dysfunctional eNOS such as uncoupling of eNOS leads to decrease in NO bioavailability and increase in superoxide anion (O₂.−) production, and in turn promotes cardiovascular diseases. Therefore, appropriate...

Université de Fribourg

Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation

Liu, Chang ; Rajapakse, Angana G. ; Riedo, Erwin ; Fellay, Benoit ; Bernhard, Marie-Claire ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Scientific Reports, 2016, vol. 6, p. 20405

Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in...

Université de Fribourg

P38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

Yu, Yi ; Rajapakse, Angana G. ; Montani, Jean-Pierre ; Yang, Zhihong ; Ming, Xiu-Fen

In: Cardiovascular Diabetology, 2014, vol. 13, no. 1, p. 113

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk...

Université de Fribourg

Arginase: the emerging therapeutic target for vascular oxidative stress and inflammation

Yang, Zhihong ; Ming, Xiu-Fen

In: Frontiers in Inflammation, 2013, vol. 4, p. 149

Oxidative stress and inflammation in the vascular wall are essential mechanisms of atherosclerosis and vascular dysfunctions associated with risk factors such as metabolic diseases, aging, hypertension, etc. Evidence has been provided that activation of the vascular endothelial cells in the presence of the risk factors promotes oxidative stress and vascular inflammatory responses, leading to...

Université de Fribourg

mTOR signalling: the molecular interface connecting metabolic stress, aging and cardiovascular diseases

Yang, Zhihong ; Ming, Xiu-Fen

In: Obesity Reviews, 2012, vol. 13, no. S2, p. 58–68

The continuing increase in the prevalence of obesity and metabolic disorders such as type-II diabetes and an accelerating aging population globally will remain the major contributors to cardiovascular mortality and morbidity in the 21st century. It is well known that aging is highly associated with metabolic and cardiovascular diseases. Growing evidence also shows that obesity and metabolic...

Université de Fribourg

Positive crosstalk between arginase-II and S6K1 in vascular endothelial inflammation and aging

Yepuri, Gautham ; Velagapudi, Srividya ; Xiong, Yuyan ; Rajapakse, Angana G. ; Montani, Jean-Pierre ; Ming, Xiu-Fen ; Yang, Zhihong

In: Aging Cell, 2012, p. -

Augmented activities of both arginase and S6K1 are involved in endothelial dysfunction in aging. This study was to investigate whether or not there is a crosstalk between arginase and S6K1 in endothelial inflammation and aging in senescent human umbilical vein endothelial cells and in aging mouse models. We show increased arginase-II (Arg-II) expression/activity in senescent endothelial cells....

Université de Fribourg

Perspectives of targeting mTORC1–S6K1 in cardiovascular aging

Ming, Xiu-Fen ; Montani, Jean-Pierre ; Yang, Zhihong

In: Frontiers in Vascular Physiology, 2012, vol. 3, p. 5

The global population aging is accelerating and age-associated diseases including cardiovascular diseases become more challenging. The underlying mechanisms of aging and age-associated cardiovascular dysfunction remain elusive. There are substantial evidences demonstrating a pivotal role of the mammalian target of rapamycin complex 1 (mTORC1) and its down-stream effector S6K1 signaling in...