Teaching and Research Department of Theories of Schools of Traditional Chinese Medicine, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People's Republic of China.
Laboratory of Anatomy, Experimental and Training Center, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People's Republic of China.
Biol Res. 2020 Sep 14;53(1):39. doi: 10.1186/s40659-020-00308-0.
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.
糖耐量受损（IGT）是一种以葡萄糖稳态缺陷为特征的代表性糖尿病前期，黄连碱（PAL）是一种具有多种药理作用的天然异喹啉生物碱。我们的研究旨在探讨 PAL 对葡萄糖耐量受损的治疗作用。
雄性 Sprague-Dawley 大鼠采用高脂肪饮食（HFD）建立 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 在体内对葡萄糖耐量受损的影响。在棕榈酸（PA）诱导的 INS-1 细胞 IGT 细胞模型中阐明了分子细节。
我们的研究表明，PAL 治疗可缓解 HFD 诱导的大鼠 IGT 并改善胰岛素抵抗。此外，PAL 治疗后胰岛功能得到改善，β细胞质量明显增加。我们进一步发现，PAL 可减轻 IGT 模型中β细胞凋亡，从而导致β细胞质量损失。此外，在体内和体外研究了 MAPK 信号通路，发现 PAL 通过限制 ERK 和 JNK 级联反应来调节 MAPK 信号通路。胰岛素分泌测定表明，PAL 通过 JNK 而不是 ERK 信号显著促进了 PA 诱导的 INS-1 细胞中缺陷的胰岛素分泌。此外，PAL 处理可显著抑制 PA 诱导的细胞中β细胞凋亡。因此，我们认为 PAL 通过抑制β细胞凋亡和 JNK 信号通路在体外促进了 PA 诱导的胰岛素释放受损。
综上所述，PAL 通过新的机制改善了 HFD 诱导的 IGT。
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