Xiong, Yuyan Yepuri, Gautham Necetin, Sevil Montani, Jean-Pierre Ming, Xiu-Fen Yang, Zhihong 2017-06-01 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. application/pdf https://folia.unifr.ch/global/documents/305554 https://folia.unifr.ch/documents/305554/files/yan_apt.pdf https://folia.unifr.ch/documents/305554/files/yan_apt_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.2337/db16-1190 info:eu-repo/semantics/openAccess License undefined Diabetes. - 2017, vol. 66, no. 6, p. 1636–1649 info:eu-repo/classification/udc/57 Arginase-II promotes tumor necrosis Factor-α release from pancreatic acinar cells causing β-cell apoptosis in aging http://purl.org/coar/resource_type/c_6501