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

  • Xiong, Yuyan Cardiovascular and Aging Research, Department of Medicine, Division of Physiology, University of Fribourg, Switzerland - Kidney Control of Homeostasis, Swiss National Centre of Competence in Research, Zurich, Switzerland
  • Yepuri, Gautham Cardiovascular and Aging Research, Department of Medicine, Division of Physiology, University of Fribourg, Switzerland
  • Necetin, Sevil Cardiovascular and Aging Research, Department of Medicine, Division of Physiology, University of Fribourg, Switzerland
  • Montani, Jean-Pierre Cardiovascular and Aging Research, Department of Medicine, Division of Physiology, University of Fribourg, Switzerland - Kidney Control of Homeostasis, Swiss National Centre of Competence in Research, Zurich, Switzerland
  • Ming, Xiu-Fen Cardiovascular and Aging Research, Department of Medicine, Division of Physiology, University of Fribourg, Switzerland - Kidney Control of Homeostasis, Swiss National Centre of Competence in Research, Zurich, Switzerland
  • Yang, Zhihong Cardiovascular and Aging Research, Department of Medicine, Division of Physiology, University of Fribourg, Switzerland - Kidney Control of Homeostasis, Swiss National Centre of Competence in Research, Zurich, Switzerland
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    01.06.2017
Published in:
  • Diabetes. - 2017, vol. 66, no. 6, p. 1636–1649
English 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 release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild- type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II−/−) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti–TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/305554
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