Waters Matthew F, Delghingaro-Augusto Viviane, Javed Kiran, Dahlstrom Jane E, Burgio Gaetan, Bröer Stefan, Nolan Christopher J
Australian National University Medical School, Australian National University, Acton, ACT 2601, Australia.
John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Metabolites. 2021 Sep 29;11(10):665. doi: 10.3390/metabo11100665.
High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD. and NOD. mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41-1.42; Mantel-Cox log rank test: = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD. and NOD. mice, respectively (ratio 1.1, 95% confidence interval 0.6-2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.
高蛋白喂养已被证明会加速雌性非肥胖糖尿病（NOD）小鼠1型糖尿病的发展。在此，我们研究了通过敲除编码系统B(0)中性氨基酸转运体AT1的基因来降低全身氨基酸可用性是否会降低雌性NOD小鼠1型糖尿病的发病率或延迟其发病。使用CRISPR-Cas9系统生成了Slc6a19基因缺陷的NOD小鼠，这导致了明显的氨基酸尿。在30周时，NOD.和NOD.小鼠的糖尿病发病率分别为59.5%（22/37）和69.0%（20/29）（风险比0.77，95%置信区间0.41-1.42；Mantel-Cox对数秩检验：P = 0.37）。无糖尿病的中位生存时间，NOD.小鼠为28周，NOD.小鼠为25周（比值1.1，95%置信区间0.6-2.0）。组织学分析未显示野生型和Slc6a19缺陷型NOD小鼠在胰岛数量或胰岛炎程度上存在差异。我们得出结论，Slc6a19缺陷并不能预防或延迟雌性NOD小鼠1型糖尿病的发展。
