Kunath Anne, Hesselbarth Nico, Gericke Martin, Kern Matthias, Dommel Sebastian, Kovacs Peter, Stumvoll Michael, Blüher Matthias, Klöting Nora
German Diabetes Center Leipzig, University of Leipzig, 04103, Leipzig, Germany.
Department of Medicine, University of Leipzig, 04103, Leipzig, Germany.
Biochem Biophys Res Commun. 2016 Sep 9;478(1):398-402. doi: 10.1016/j.bbrc.2016.07.038. Epub 2016 Jul 9.
Replication initiator 1 (Repin1) is a zinc finger protein playing a role in insulin sensitivity, body fat mass and lipid metabolism by regulating the expression key genes of glucose and lipid metabolism. Here, we tested the hypothesis that introgression of a Repin1 deletion into db/db mice improves glucose metabolism in vivo. We generated a whole body Repin1 deficient db/db double knockout mouse (Rep1(-/-)x db/db) and systematically characterized the consequences of Repin1 deficiency on insulin sensitivity, glucose and lipid metabolism parameters and fat mass. Hyperinsulinemic-euglycemic clamp studies revealed significantly improved insulin sensitivity in Rep1(-/-)x db/db mice, which are also characterized by lower HbA1c, lower body fat mass and reduced adipose tissue (AT) inflammation area. Our study provides evidence that loss of Repin1 in db/db mice improves insulin sensitivity and reduces chronic hyperglycemia most likely by reducing fat mass and AT inflammation.
复制起始因子1（Repin1）是一种锌指蛋白，通过调节葡萄糖和脂质代谢的关键基因表达，在胰岛素敏感性、体脂量和脂质代谢中发挥作用。在此，我们验证了一个假说，即将Repin1缺失基因导入db/db小鼠体内可改善其体内葡萄糖代谢。我们培育出了全身Repin1基因缺陷的db/db双敲除小鼠（Rep1(-/-)x db/db），并系统地研究了Repin1基因缺陷对胰岛素敏感性、葡萄糖和脂质代谢参数以及脂肪量的影响。高胰岛素-正常血糖钳夹研究表明，Rep1(-/-)x db/db小鼠的胰岛素敏感性显著提高，其特征还包括较低的糖化血红蛋白、较低的体脂量和减小的脂肪组织（AT）炎症面积。我们的研究提供了证据，表明db/db小鼠中Repin1的缺失最有可能通过减少脂肪量和AT炎症来提高胰岛素敏感性并降低慢性高血糖水平。
