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Endocrinol."],"abstract":"<jats:p>Obesity plays a major role in type II diabetes (T2DM) progression because it applies metabolic and oxidative stress resulting in dysfunctional beta-cells and activation of intra-islet pancreatic stellate cells (PaSCs) which cause islet fibrosis. Administration of antioxidant N-acetyl-L-cysteine (NAC) <jats:italic>in vivo<\/jats:italic> improves metabolic outcomes in diet-induced obese diabetic mice, and <jats:italic>in vitro<\/jats:italic> inhibits PaSCs activation. However, the effects of NAC on diabetic islets <jats:italic>in vivo<\/jats:italic> are unknown. This study examined if dosage and length of NAC treatment in HFD-induced diabetic mice effect metabolic outcomes associated with maintaining healthy beta-cells and quiescent PaSCs, <jats:italic>in vivo<\/jats:italic>. Male C57BL\/6N mice were fed normal chow (ND) or high-fat (HFD) diet up to 30 weeks. NAC was administered in drinking water to HFD mice in preventative treatment (HFD<jats:sup>pNAC<\/jats:sup>) for 23 weeks or intervention treatment for 10 (HFD<jats:sup>iNAC<\/jats:sup>) or 18 (HFD<jats:sup>iNAC+)<\/jats:sup> weeks, respectively. HFD<jats:sup>pNAC<\/jats:sup> and HFD<jats:sup>iNAC+<\/jats:sup>, but not HFD<jats:sup>iNAC<\/jats:sup>, mice showed significantly improved glucose tolerance and insulin sensitivity. Hyperinsulinemia led by beta-cell overcompensation in HFD mice was significantly rescued in NAC treated mice. A reduction of beta-cell nuclear Pdx-1 localization in HFD mice was significantly improved in NAC treated islets along with significantly reduced beta-cell oxidative stress. HFD-induced intra-islet PaSCs activation, labeled by \u03b1SMA, was significantly diminished in NAC treated mice along with lesser intra-islet collagen deposition. This study determined that efficiency of NAC treatment is beneficial at maintaining healthy beta-cells and quiescent intra-islet PaSCs in HFD-induced obese T2DM mouse model. These findings highlight an adjuvant therapeutic potential in NAC for controlling T2DM progression in humans.<\/jats:p>","DOI":"10.3389\/fendo.2022.938680","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T05:14:11Z","timestamp":1661404451000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["N-acetyl-L-cysteine treatment reduces beta-cell oxidative stress and pancreatic stellate cell activity in a high fat diet-induced diabetic mouse 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