Long Kexin, Chen Wangqing, Mao Manyun, Zhu Wu
Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008.
Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha 410008.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025 Mar 28;50(3):344-357. doi: 10.11817/j.issn.1672-7347.2025.240619.
Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis.
HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro.
Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes and . Transcription of gluconeogenesis-related gene decreased, while transcription levels of glycogen synthesis-related genes and increased (all <0.05), while acitretin inhibits glucose uptake and promotes gluconeogenesis in low-glucose environment. In vivo experiments revealed that compared with the control group, the blood glucose level in the IMQ group was significantly decreased (<0.05), while acitretin treatment partially restored glucose homeostasis and alleviated weight loss. Ex vivo culture of islets from psoriatic mice revealed that acitretin reduced elevated insulin secretion and downregulated expression, while upregulating glucose homeostasis gene and insulin sensitivity gene (all <0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis.
Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.
银屑病是一种慢性炎症性皮肤病，常伴有高血糖、胰岛素抵抗和肥胖等合并症。阿维A作为第二代维甲酸，用于治疗银屑病。本研究旨在探讨阿维A在银屑病患者糖脂代谢中的作用。
在高糖或低糖条件下用阿维A处理HepG2细胞。使用实时逆转录PCR（实时RT-PCR）和蛋白质印迹法评估葡萄糖转运相关基因的mRNA和蛋白质表达水平。通过流式细胞术分析葡萄糖摄取，并通过油红O染色评估细胞内脂滴形成。将健康成年雌性BALB/C小鼠随机分为3组：对照组、咪喹莫特（IMQ）诱导的银屑病模型组（IMQ组）和阿维A治疗组。检查皮肤病变和炎症标志物，以及体重、血浆葡萄糖/脂质水平和代谢基因转录的变化。从正常和银屑病诱导的小鼠中分离胰岛，并在体外评估阿维A对胰岛素分泌的影响。
阿维A处理增加了高糖环境下HepG2细胞的葡萄糖摄取和脂滴合成，葡萄糖转运相关基因 和 的转录水平升高。糖异生相关基因 的转录减少，而糖原合成相关基因 和 的转录水平增加（均<0.05），而阿维A在低糖环境中抑制葡萄糖摄取并促进糖异生。体内实验表明，与对照组相比，IMQ组的血糖水平显著降低（<0.05），而阿维A治疗部分恢复了葡萄糖稳态并减轻了体重减轻。对银屑病小鼠胰岛的体外培养表明，阿维A降低了升高的胰岛素分泌并下调了 表达，同时上调了葡萄糖稳态基因 和胰岛素敏感性基因 （均<0.05）。这些发现表明阿维A在改善胰岛功能和恢复胰岛稳态中起关键作用。
阿维A有助于维持肝脏糖原生成和糖异生之间的平衡，增强胰岛素敏感性，改善胰岛功能，从而促进全身和细胞的葡萄糖稳态。
