Department of Biological Sciences, North Dakota State University, Fargo, ND 58108, USA.
Gen Comp Endocrinol. 2012 Jan 15;175(2):321-8. doi: 10.1016/j.ygcen.2011.11.029. Epub 2011 Nov 29.
Many species of fish, including rainbow trout, possess multiple INS- and IR-encoding mRNAs. In this study, rainbow trout (Oncorhynchus mykiss) were used as a model to study the regulation of INS (INS1, INS2) and IR (IR1, IR2, IR3, and IR4) mRNA expression by nutritional state and glucose. In the nutritional state study, fish were either fed continuously, fasted (4 or 6 weeks), or fasted 4 weeks, then refed for 2 weeks. Nutritional state regulated INS and IR mRNA expression in a subtype- and tissue-specific manner. A 4-week fast reduced INS1 expression in endocrine pancreas (Brockmann body) and of INS1 and INS2 in brain, whereas a 6-week fast reduced the expression of both INS1 and INS2 in pancreas but only of INS1 in brain. Refeeding only restored INS2 levels in pancreas. In adipose tissue, by contrast, a 4-week fast increased INS1 expression, and a 6-week fast increased the expression of both INS1 and INS2. Nutritional state also modulated the pattern of IR mRNA expression. Fasting for 4 weeks resulted in no significant change in IR expression. Prolonged fasting (6 weeks) increased the expression of IR4 mRNA in the pancreas, adipose tissue, cardiac muscle, and gill; however, fasting decreased expression of IR3 mRNA in liver. Refeeding restored fasting-associated increases in IR4 expression in pancreas, adipose tissue, cardiac muscle, and gill, but had no effect on the fasting-associated decrease in IR3 expression in liver. Glucose differentially regulated the expression of INS and IR mRNAs in Brockmann bodies and liver pieces incubated in vitro, respectively. Low glucose (1 mM) reduced pancreatic expression of both INS1 and INS2 mRNAs compared to levels observed at 4 or 10 mM glucose. In the liver, IR1 and IR2 mRNA expression was insensitive to glucose concentration, whereas expression of IR3 and IR4 was attenuated at 1 and 10 mM compared to 4 mM glucose. These findings indicate that the pattern of INS and IR expression in selected tissues is regulated by nutritional state and glucose.
许多鱼类物种,包括虹鳟鱼,拥有多种 INS 和 IR 编码的 mRNAs。在这项研究中,虹鳟鱼(Oncorhynchus mykiss)被用作模型来研究营养状态和葡萄糖对 INS(INS1、INS2)和 IR(IR1、IR2、IR3 和 IR4)mRNA 表达的调节。在营养状态研究中,鱼要么连续喂食,要么禁食(4 或 6 周),要么禁食 4 周,然后再喂食 2 周。营养状态以亚型和组织特异性的方式调节 INS 和 IR mRNA 的表达。4 周的禁食减少了内分泌胰腺(Brockmann 体)中 INS1 的表达以及大脑中 INS1 和 INS2 的表达,而 6 周的禁食减少了胰腺中两种 INS1 和 INS2 的表达,但仅减少了大脑中 INS1 的表达。再喂食仅恢复了胰腺中 INS2 的水平。相反,在脂肪组织中,4 周的禁食增加了 INS1 的表达,而 6 周的禁食增加了 INS1 和 INS2 的表达。营养状态也调节了 IR mRNA 表达的模式。4 周的禁食对 IR 表达没有显著影响。长期禁食(6 周)增加了胰腺、脂肪组织、心肌和鳃中的 IR4 mRNA 的表达;然而,禁食降低了肝脏中 IR3 mRNA 的表达。再喂食恢复了禁食引起的胰腺、脂肪组织、心肌和鳃中 IR4 表达的增加,但对肝脏中禁食引起的 IR3 表达的减少没有影响。葡萄糖分别在体外孵育的 Brockmann 体和肝片中差异调节 INS 和 IR mRNAs 的表达。与在 4 或 10 mM 葡萄糖下观察到的水平相比,低葡萄糖(1 mM)降低了胰腺中两种 INS1 和 INS2 mRNAs 的表达。在肝脏中,IR1 和 IR2 mRNA 的表达对葡萄糖浓度不敏感,而 IR3 和 IR4 的表达在 1 和 10 mM 时与 4 mM 葡萄糖相比减弱。这些发现表明,选定组织中 INS 和 IR 表达的模式受营养状态和葡萄糖的调节。