Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice.
Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice.
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恩格列净和利格列汀的早期联合治疗对糖尿病db/db小鼠的胰腺β细胞产生有益作用。
DOI：
10.1038/s41598-021-94896-w
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发表时间：
2021-08-09
影响因子：
4.6
通讯作者：
Kaneto H
中科院分区：
文献类型：
--
作者：
Fushimi Y;Obata A;Sanada J;Nogami Y;Ikeda T;Yamasaki Y;Obata Y;Shimoda M;Nakanishi S;Mune T;Kaku K;Kaneto H
二肽基肽酶-4（DPP-4）抑制剂和钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂联合治疗对β细胞的影响尚不清楚，尽管这两种药物的联合用药在临床实践中已很常见。因此，我们的目的是阐明DPP-4抑制剂和/或SGLT 2抑制剂对β细胞质量和功能的影响，并比较它们在糖尿病早期和晚期的影响。我们使用7周龄db/db小鼠作为早期阶段，使用16周龄小鼠作为晚期阶段，并经口给予利格列汀、恩格列净、利格列汀+恩格列净（L + E组）和0.5%羧甲基纤维素（对照组）治疗2周。恩格列净组和L + E组治疗后血糖水平明显低于对照组。此外，L + E组的β细胞团仅在早期显著大于Cont组，并伴有Ki 67阳性β细胞比率增加。在离体胰岛中，胰岛素及其转录因子的mRNA表达水平在早期阶段仅在L + E组中显著升高。此外，与β细胞分化和增殖相关的mRNA表达水平仅在L + E组早期显著增加。总之，DPP-4抑制剂和SGLT 2抑制剂联合给药对β细胞质量和功能具有更有益的影响，尤其是在糖尿病早期而非晚期。
Effects of combination therapy of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor on β-cells are still unclear, although combination agent of these two drugs has become common in clinical practice. Therefore, we aimed to elucidate the effects of DPP-4 inhibitor and/or SGLT2 inhibitor on β-cell mass and function and compared their effects between in an early and advanced phase of diabetes. We used 7-week-old db/db mice as an early phase and 16-week-old mice as an advanced phase and treated them for 2 weeks with oral administration of linagliptin, empagliflozin, linagliptin + empagliflozin (L + E group), and 0.5% carboxymethylcellulose (Cont group). Blood glucose levels in Empa and L + E group were significantly lower than Cont group after treatment. In addition, β-cell mass in L + E group was significantly larger than Cont group only in an early phase, accompanied by increased Ki67-positive β-cell ratio. In isolated islets, mRNA expression levels of insulin and its transcription factors were all significantly higher only in L + E group in an early phase. Furthermore, mRNA expression levels related to β-cell differentiation and proliferation were significantly increased only in L + E group in an early phase. In conclusion, combination of DPP-4 inhibitor and SGLT2 inhibitor exerts more beneficial effects on β-cell mass and function, especially in an early phase of diabetes rather than an advanced phase.
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影响因子：
7.7
作者：
Lingohr, MK;Dickson, LM;Rhodes, CJ
通讯作者：
Rhodes, CJ
影响因子：
15.9
作者：
NAUCK, MA;HEIMESAAT, MM;CREUTZFELDT, W
通讯作者：
CREUTZFELDT, W
DOI：
10.1111/dom.12005
发表时间：
2013-02
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Hamamoto S;Kanda Y;Shimoda M;Tatsumi F;Kohara K;Tawaramoto K;Hashiramoto M;Kaku K
通讯作者：
Kaku K
影响因子：
15.9
作者：
Hennige, AM;Burks, DJ;White, MF
通讯作者：
White, MF
DOI：
10.1124/jpet.114.213454
发表时间：
2014-09-01
影响因子：
3.5
作者：
Hansen, Henrik H.;Jelsing, Jacob;Mayoux, Eric
通讯作者：
Mayoux, Eric