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

Autor: Fushimi, Yoshiro, Obata, Atsushi, Sanada, Junpei, Nogami, Yuka, Ikeda, Tomoko, Yamasaki, Yuki, Obata, Yoshiyuki, Shimoda, Masashi, Nakanishi, Shuhei, Mune, Tomoatsu, Kaku, Kohei, Kaneto, Hideaki
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Zdroj: Scientific Reports; 8/9/2021, Vol. 11 Issue 1, p1-13, 13p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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