摘要
2型糖尿病(type 2 diabetes mellitus,T2DM)是一种以持续高血糖和胰岛素抵抗为主要特征的常见慢性代谢性疾病。在胰腺β细胞中,糖促胰岛素分泌(glucose-stimulated insulin secretion,GSIS)对于维持机体血糖平衡具有非常重要的作用。前期研究发现中药栀子活性成分京尼平苷可快速调节胰腺β细胞对葡萄糖的吸收、代谢和葡萄糖诱导胰岛素分泌,但具体作用机制还有待探索。由于葡萄糖转运体(glucose transporter,GLUT)糖基化对于其感受细胞微环境改变,调节葡萄糖稳态起关键作用。该文探究了京尼平苷对胰腺β细胞中GLUT2糖基化关键分子的影响,结果证实,京尼平苷能够显著上调GlcNAcT-Ⅳa糖基化转移酶(GlcNAcT-Ⅳa glycosyltransferase,GnT-Ⅳa)和半乳凝集素9(galectin-9)mRNA和蛋白的水平,但对网格蛋白clathrin表达水平无明显影响;在低、中糖浓度条件下,京尼平苷短时间内(1 h)对GnT-Ⅳa蛋白的水平有显著调节作用,但对galectin-9蛋白水平无明显的影响。并且,京尼平苷还可以在短时间内显著影响糖基化GLUT2蛋白的水平。上述研究结果提示,京尼平苷可快速调节INS-1大鼠胰腺β细胞中糖基化关键分子GnT-Ⅳa蛋白的水平,影响GLUT2糖基化。这些研究结果提示,京尼平苷调节胰腺β细胞对葡萄糖的吸收、代谢和糖促胰岛素分泌可能与其调节GLUT2糖基化,影响其在细胞膜上的分布有关。
Type 2 diabetes mellitus(T2DM)is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance.In pancreaticβ-cells,glucose-stimulated insulin secretion(GSIS)plays a pivotal role in maintaining the balance of blood glucose level.Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreaticβcells,but the specific mechanism needs to be further explored.Emerging evidence indicated that glycosylation of glucose transporter(GLUT)has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells.In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreaticβcells.The results showed that geniposide could significantly up-regulate the mRNA and protein levels of GlcNAcT-Ⅳa glycosyltransferase(GnT-Ⅳa)and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of GnT-Ⅳa in a short time(1 h)under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9.In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment.The above results suggested that geniposide could quickly regulate the protein level of GnT-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreaticβcells and affect the glycosylation of GLUT2.These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreaticβcells.
作者
蒋孝清
申甚莉
李维钊
徐星科
殷菲
JIANG Xiao-qing;SHEN Shen-li;LI Wei-zhao;XU Xing-ke;YIN Fei(Chongqing Key Laboratory of Medicinal Chemistry&Molecular Pharmacology,Chongqing 400054,China;School of Pharmacy&Bioengineering,Chongqing University of Technology,Chongqing 400054,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2021年第14期3643-3649,共7页
China Journal of Chinese Materia Medica
基金
重庆市自然科学基金重点项目(2017jcyjB0077)
重庆市高校优秀创新团队项目(CXTDX201601031)。
