Combination therapy of systemic and local metformin improves imiquimod-induced psoriasis-like lesions with type 2 diabetes: the role of AMPK/KGF/STAT3 axis.

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2024-10-24 DOI:10.1080/13813455.2024.2407547

Fatma ElSayed Hassan, Basma Emad Aboulhoda, Marwa Nagi Mehesen, Passant Mohie El Din, Hend Ahmed Abdallah, Ehab R Bendas, Laila Ahmed Rashed, Abeer Mostafa, Marwa Fathy Amer, Marwa Abdel-Rahman, Mansour A Alghamdi, Asmaa Mohammed Shams Eldeen

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Abstract

Context: Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO).

Objectives: We investigated potential therapeutic mechanisms of metformin in a murine animal model of psoriasiform lesions in T2DM.

Materials and methods: Forty-two rats were randomly divided into control, PsO, and type II DM (T2DM) groups. After confirmation of DM, the type II diabetic rats were allocated into T2DM+ PsO, T2DM+ PsO+ systemic metformin (S. met), T2DM+ PsO+ topical metformin (T. met)), and T2DM+ PsO + combined metformin (C. met). PsO was induced by topical imiquimod.

Results: Systemic administration of the cornerstone antidiabetic drug, metformin, was able to improve insulin resistance and lipid profile. At molecular levels, both topical and systemic metformin significantly increased AMP-activated protein kinase (AMPK), and lowered keratinocyte growth factor (KGF) / "Signal transducer and activator of transcription" (STAT)3 protein levels, and the IL-17RA and IL-17RC gene expression.

Conclusion: Although its glucose-controlling effect was not optimum, T.met gel served anti-psoriatic and anti-inflammatory effects.

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全身和局部二甲双胍联合疗法可改善咪喹莫特诱导的 2 型糖尿病银屑病样皮损：AMPK/KGF/STAT3 轴的作用。

背景：胰岛素抵抗和血脂紊乱是2型糖尿病（T2DM）和不同皮肤病，尤其是银屑病（PsO）的常见并发症：我们研究了二甲双胍在 T2DM 银屑病皮损小鼠动物模型中的潜在治疗机制：42只大鼠被随机分为对照组、银屑病组和II型DM（T2DM）组。确认为 DM 后，II 型糖尿病大鼠被分为 T2DM+ PsO 组、T2DM+ PsO+ 全身二甲双胍组（S. met）、T2DM+ PsO+ 局部二甲双胍组（T. met）和 T2DM+ PsO+ 联合二甲双胍组（C. met）。PsO由局部咪喹莫特诱导：结果：全身应用基础抗糖尿病药物二甲双胍能够改善胰岛素抵抗和血脂状况。在分子水平上，局部和全身使用二甲双胍都能显著增加AMP激活蛋白激酶（AMPK），降低角质细胞生长因子（KGF）/"信号转导和激活转录"（STAT）3蛋白水平以及IL-17RA和IL-17RC基因表达：结论：虽然T.met凝胶的控糖效果并不理想，但它具有抗银屑病和抗炎作用。

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

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.