Effect of the SGLT2 inhibitor ipragliflozin on the expression of genes that regulate skin function.

IF 3.2 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Diabetic Medicine Pub Date : 2024-12-22 DOI:10.1111/dme.15505

Nobutomo Ikarashi, Keito Tabata, Yui Shinozaki, Risako Kon, Hiroyasu Sakai, Tomoo Hosoe

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引用次数: 0

Abstract

Aims: Skin disorders occur more frequently with sodium-dependent glucose cotransporter type 2 (SGLT2) inhibitors than with other antidiabetic drugs. We conducted basic research using ipragliflozin, with the aim of identifying new measures to prevent skin disorders caused by SGLT2 inhibitors.

Methods: db/db type 2 diabetes model mice were orally administered ipragliflozin (10 mg/kg or 30 mg/kg) once a day for 28 days and skin function genes were analysed by real-time RT-PCR or Western blotting.

Results: No difference in the expression level of collagen (Col1a1 and Col1a2) in the skin was detected between the ipragliflozin treatment group and the control group. On the other hand, the expression levels of enzymes involved in the synthesis and decomposition of hyaluronic acid (Has2 and Hayl1) and enzymes involved in the synthesis and decomposition of ceramide (Sptlc1, Sptlc2, Asah1, and Acer1) were significantly decreased by the administration of ipragliflozin. Furthermore, the expression levels of filaggrin (Flg), loricrin (Lor), elastin (Eln), and aquaporin-3 (Aqp3) in the skin were lower in the ipragliflozin treatment group than in the control group.

Conclusions: It was revealed that ipragliflozin reduces the expression of genes involved in skin barrier and moisturizing functions, which this may be one of the mechanisms through which this drug causes skin disorders.

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SGLT2抑制剂ipragliflozin对皮肤功能调控基因表达的影响。

目的：与其他降糖药相比，钠依赖性葡萄糖共转运蛋白2型（SGLT2）抑制剂更容易发生皮肤疾病。我们使用ipragliflozin进行了基础研究，目的是确定预防SGLT2抑制剂引起的皮肤疾病的新措施。方法：db/db 2型糖尿病模型小鼠口服伊普列净（10 mg/kg或30 mg/kg），每天1次，连续28 d，采用实时RT-PCR或Western blotting分析皮肤功能基因。结果：ipragliflozin治疗组与对照组皮肤胶原蛋白（Col1a1、Col1a2）表达水平无差异。另一方面，服用ipragliflozin后，参与透明质酸合成和分解的酶（Has2和Hayl1）和参与神经酰胺合成和分解的酶（Sptlc1、Sptlc2、Asah1和Acer1）的表达水平显著降低。此外，伊普列净治疗组皮肤中聚丝蛋白（Flg）、loricrin （Lor）、弹性蛋白（Eln）和水通道蛋白-3 （Aqp3）的表达水平低于对照组。结论：ippragliflozin可降低参与皮肤屏障和保湿功能的基因的表达，这可能是该药物引起皮肤疾病的机制之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetic Medicine 医学-内分泌学与代谢

CiteScore

7.20

自引率

5.70%

发文量

229

审稿时长

3-6 weeks

期刊介绍： Diabetic Medicine, the official journal of Diabetes UK, is published monthly simultaneously, in print and online editions. The journal publishes a range of key information on all clinical aspects of diabetes mellitus, ranging from human genetic studies through clinical physiology and trials to diabetes epidemiology. We do not publish original animal or cell culture studies unless they are part of a study of clinical diabetes involving humans. Categories of publication include research articles, reviews, editorials, commentaries, and correspondence. All material is peer-reviewed. We aim to disseminate knowledge about diabetes research with the goal of improving the management of people with diabetes. The journal therefore seeks to provide a forum for the exchange of ideas between clinicians and researchers worldwide. Topics covered are of importance to all healthcare professionals working with people with diabetes, whether in primary care or specialist services. Surplus generated from the sale of Diabetic Medicine is used by Diabetes UK to know diabetes better and fight diabetes more effectively on behalf of all people affected by and at risk of diabetes as well as their families and carers.”