Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice

被引：13

作者：

Fushimi, Yoshiro ^{[1
]}

Obata, Atsushi ^{[1
]}

Sanada, Junpei ^{[1
]}

Nogami, Yuka ^{[1
]}

Ikeda, Tomoko ^{[1
]}

Yamasaki, Yuki ^{[2
]}

Obata, Yoshiyuki ^{[1
]}

Shimoda, Masashi ^{[1
]}

Nakanishi, Shuhei ^{[1
]}

Mune, Tomoatsu ^{[1
]}

Kaku, Kohei ^{[1
]}

Kaneto, Hideaki ^{[1
]}

机构：

[1] Kawasaki Med Sch, Dept Diabet Endocrinol & Metab, 577 Matsushima, Kurashiki, Okayama 7010192, Japan

[2] Kawasaki Univ Med Welf, Dept Clin Nutr, 288 Matsushima, Kurashiki, Okayama 7010193, Japan

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

基金：

日本学术振兴会;

关键词：

JAPANESE PATIENTS; DIPEPTIDYL PEPTIDASE-4; RECEPTOR EXPRESSION; INSULIN-RESISTANCE; DOWN-REGULATION; INHIBITORS; PRESERVES; MASS; REDUCTION; EFFICACY;

D O I：

10.1038/s41598-021-94896-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Effects of combination therapy of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor on beta-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 beta-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, beta-cell mass in L + E group was significantly larger than Cont group only in an early phase, accompanied by increased Ki67-positive beta-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 beta-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 beta-cell mass and function, especially in an early phase of diabetes rather than an advanced phase.

引用

页数：13