Differential effects of sodium-glucose cotransporter 2 inhibitor and low-carbohydrate diet on body composition and metabolic profile in obese diabetic db/db mice
Differential effects of sodium-glucose cotransporter 2 inhibitor and low-carbohydrate diet on body composition and metabolic profile in obese diabetic db/db mice
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DOI：
10.1136/bmjdrc-2020-001303
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发表时间：
2020-01-01
影响因子：
4.1
通讯作者：
Satoh-Asahara, Noriko
中科院分区：
文献类型：
--
作者：
Kusakabe, Toru;Yokota, Shigefumi;Satoh-Asahara, Noriko
介绍使用钠-葡萄糖协同转运蛋白（SGLT）2抑制剂和低碳水化合物饮食（LCD）治疗肥胖和2型糖尿病在碳水化合物限制方面是相似的。然而，它们的作用机制不同，对身体的影响仍不清楚。本研究采用肥胖和2型糖尿病db/db小鼠模型，研究SGLT 2抑制剂和LCD对肥胖和2型糖尿病db/db小鼠体成分和代谢的影响。研究设计和方法将8周龄雄性db/db小鼠分为4组：正常饮食和给予溶媒或卡格列净（Cana）的小鼠和给予LCD和给予溶媒或Cana 8周的小鼠。结果Cana给药和LCD喂养均导致体重显著增加。Cana给药显著降低了血浆葡萄糖水平并增加了血浆胰岛素水平，同时保留了胰腺β细胞。然而，LCD喂养并没有改善血糖水平，但恶化了胰岛素敏感性。LCD喂养显着降低了肝脏重量和肝脏甘油三酯含量;使用Cana时未观察到这些影响。结论SGLT 2抑制剂和LCD对机体的影响不同。它们的联合使用可以更好地改善肥胖和2型糖尿病的代谢。
Introduction Treatment using sodium-glucose cotransporter (SGLT) 2 inhibitor and low-carbohydrate diet (LCD) for obesity and type 2 diabetes are similar in terms of carbohydrate limitation. However, their mechanisms of action differ, and the effects on the body remain unclear. We investigated the effects of SGLT2 inhibitor and LCD on body composition and metabolic profile using thedb/dbmouse model for obesity and type 2 diabetes.Research design and methods Eight-week-old maledb/dbmice were divided into four groups: mice receiving normal diet and vehicle or canagliflozin (Cana) administration and mice receiving LCD and vehicle or Cana administration for 8 weeks. Consumed calories were adjusted to be equal among the groups.Results Both Cana administration and LCD feeding resulted in significant weight gain. Cana administration significantly decreased plasma glucose levels and increased plasma insulin levels with preservation of pancreatic beta cells. However, LCD feeding did not improve plasma glucose levels but deteriorated insulin sensitivity. LCD feeding significantly reduced liver weight and hepatic triglyceride content; these effects were not observed with Cana administration. Combined treatment with LCD did not lead to an additive increase in blood beta-ketone levels.Conclusions SGLT2 inhibitors and LCD exert differential effects on the body. Their combined use may achieve better metabolic improvements in obesity and type 2 diabetes.