Metabolic effects of Tofogliflozin are efficiently enhanced with appropriate dietary carbohydrate ratio and are distinct from carbohydrate restriction.
Metabolic effects of Tofogliflozin are efficiently enhanced with appropriate dietary carbohydrate ratio and are distinct from carbohydrate restriction.
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DOI：
10.14814/phy2.13642
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发表时间：
2018-03
影响因子：
2.5
通讯作者：
Ishida H
中科院分区：
文献类型：
--
作者：
Ito S;Hosaka T;Yano W;Itou T;Yasumura M;Shimizu Y;Kobayashi H;Nakagawa T;Inoue K;Tanabe S;Kondo T;Ishida H
钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT2i) 通过促进尿葡萄糖排泄发挥抗糖尿病作用。营养治疗显然很重要，但人们对 SGLT2i 药物与碳水化合物限制之间的相互作用知之甚少。因此，我们使用肥胖糖尿病动物模型研究了这些相互作用。 KK-Ay 小鼠采用正常饲料配对喂养 [NC;碳水化合物：脂肪：蛋白质=65:15:20]，低碳水化合物[LC； 43:42:15]或严格限制碳水化合物饮食[SR； 12:45:43] 12 周。 Tofogliflozin (Tofo) 在 NC 和 LC 饮食组中作为 SGLT2i 施用。 SR组的血糖水平显着升高。 Tofo 在实验期间显着降低了 NC 组的血糖水平，并在 2-6 周时显着降低了 LC 组的血糖水平。未服用 Tofo 的 SR 组血浆甘油三酯显着升高，但服用 Tofo 后血浆甘油三酯下降。单独使用 LC 或 SR 饮食不会改变肝脏甘油三酯含量。然而，Tofo 可改善 NC 喂养动物的肝脂肪变性。与硬脂酰辅酶A去饱和酶 1 的下调一致，在使用 Tofo 的 LC 组和仅使用 SR 组中，血浆单不饱和脂肪酸与饱和脂肪酸的比率显着降低，但在使用 Tofo 的 NC 组中没有改变。总之，Tofo 改善了葡萄糖和脂质的代谢，但 SR 饮食则没有改善。此外，与 LC 饮食组相比，Tofo 在 NC 饮食组中更有效地改善了这些参数。这些数据表明，SGLT2i 的效果与碳水化合物限制的效果不同，并且非限制性饮食碳水化合物组成对于 SGLT2i 治疗有效至关重要。
Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) exert their antidiabetic effects by promoting urinary glucose excretion. Nutrition therapy is obviously important, but little is known about the interactions between SGLT2i agents and carbohydrate restriction. Therefore, we studied these interactions using an obese diabetic animal model. KK‐Ay mice were pair‐fed normal chow [NC; carbohydrate: fat: protein = 65:15:20], low carbohydrate [LC; 43:42:15] or severely carbohydrate restricted diets [SR; 12:45:43] for 12 weeks. Tofogliflozin (Tofo) was administered as the SGLT2i in the NC and LC diet groups. Blood glucose levels were significantly increased in the SR group. Tofo reduced blood glucose levels significantly in the NC group during the experiment and in the LC group at 2‐6 weeks. Plasma triglycerides were markedly elevated in the SR group without Tofo, but decreased in response to Tofo administration. Hepatic triglyceride contents were not changed by the LC or the SR diet alone. However, Tofo ameliorated hepatosteatosis in NC‐fed animals. Consistent with the downregulation of stearoyl‐CoA desaturase 1, the ratio of plasma monounsaturated to saturated fatty acids was significantly reduced in the LC with Tofo and in the SR alone groups, but was not altered in the NC with Tofo group. In summary, metabolism of glucose and lipids was improved by Tofo but not by the SR diet. Furthermore, Tofo improved these parameters more effectively in the NC than in the LC diet group. These data suggest that the effects of SGLT2i are distinct from those of carbohydrate restriction and that a nonrestricted dietary carbohydrate composition is essential for SGLT2i treatment to be effective.