| First Author | Xiong Y | Year | 2017 |
| Journal | Diabetes | Volume | 66 |
| Issue | 6 | Pages | 1636-1649 |
| PubMed ID | 28356309 | Mgi Jnum | J:246638 |
| Mgi Id | MGI:5923060 | Doi | 10.2337/db16-1190 |
| Citation | Xiong Y, et al. (2017) Arginase-II Promotes Tumor Necrosis Factor-alpha Release From Pancreatic Acinar Cells Causing beta-Cell Apoptosis in Aging. Diabetes 66(6):1636-1649 |
| abstractText | 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 beta-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 beta-cell mass, and more proliferative and less apoptotic beta-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-alpha (TNF-alpha). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II-/-) mice contains higher TNF-alpha levels than the young mice and stimulates beta-cell apoptosis and dysfunction, which are prevented by a neutralizing anti-TNF-alpha antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-alpha release through p38 MAPK leading to beta-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice. |
