The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. Male Sprague–Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased β cell mass after the treatment of PAL. We further found out that PAL could alleviate the β cell apoptosis that accounts for β cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress β cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the β cell apoptosis and JNK signaling in vitro. In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.

中文翻译：

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棕榈碱可改善高脂饮食引起的糖耐量降低。

葡萄糖耐量降低（IGT）是典型的糖尿病前兆，其特征是葡萄糖稳态失调，而棕榈碱（PAL）是天然的异喹啉生物碱，具有多种药理作用。我们的研究旨在研究PAL对糖耐量受损的治疗作用。使用雄性Sprague–Dawley大鼠建立高脂饮食（HFD）的IGT模型。进行口服葡萄糖耐量试验（OGTT）和进一步的生化分析，以确定PAL对体内葡萄糖耐量的影响。在INS-1细胞上由棕榈酸酯（PA）诱导的IGT细胞模型中阐明了分子细节。我们的研究表明，在PAL治疗后，HFD诱导的大鼠IGT可以改善胰岛素抵抗。除了，PAL治疗后，β细胞量显着增加，证实了胰岛功能的增强。我们进一步发现，PAL可以减轻占IGT模型中β细胞质量损失的β细胞凋亡。此外，在体内和体外对MAPK信号进行了研究，发现PAL通过限制ERK和JNK级联来调节MAPK信号。胰岛素分泌测定表明，PAL通过JNK而非ERK信号转导显着促进了PA诱导的INS-1细胞中的胰岛素分泌缺陷。此外，已确定PAL处理可显着抑制PA诱导的细胞中的β细胞凋亡。因此，我们认为PAL通过在体外抑制β细胞凋亡和JNK信号传导来促进PA诱导的胰岛素释放受损。综上所述，