低糖状态对大鼠增食欲素及受体的影响

Effect of Hypoglycemia on the Orexin and Their Receptors in Rat

目的 研究急性葡萄糖水平的下降对大鼠下丘脑及培养胰岛细胞中增食欲素 (orexin)及其受体(OX1 R、OX2 R)的影响。方法 应用单次皮下注射胰岛素并伴 (或不伴 )禁食的方法 ,构建急性低血糖大鼠模型 ;体外原代培养胰岛细胞并调整培养液的葡萄糖浓度 (8 3mmol L及 2 8mmol L) ;应用反转录 -聚合酶链反应 (RT PCR)检测下丘脑组织和胰岛细胞中orexin系统的变化。结果 在胰岛素 (伴禁食 )诱导的急性低血糖大鼠模型中 ,下丘脑orexin的mRNA表达较对照组增加约 1 5 0 % (P <0 0 1 ) ,OX1 R的mRNA表达减少 30 % (P <0 0 1 ) ,但是OX2 R的mRNA表达没有明显变化 (P >0 0 5 ) ;在培养胰岛细胞体外实验中 ,培养基中葡萄糖浓度由 8 3降至 2 8mmol L ,6h后胰岛细胞的orexinmRNA表达增加 1 0 0 % (P <0 0 1 ) ,而OX1 RmRNA表达对培养基中葡萄糖浓度的急性波动不敏感。结论 急性葡萄糖水平降低将刺激大鼠下丘脑中orexin的表达 ,其受体的变化相反 ;进食将会抑制orexin系统的这一反应。

Objective To study the effect of glucose change on expression of prepro orexin and its receptors, orexin 1 receptor (OX 1R) and orexin 2 receptor (OX 2R) in rat hypothalamus tissue and pancreatic islets cells. Methods The acute hypoglycemia rat model was induced by subcutaneous injection of insulin. The effect of 2 8 mmol/L and 8 3mmol/L glucose on pancreatic islet cell orexin system was detected in pancreas islet cell culture. The expression of prepro orexin and OXR mRNA was examined by reverse transcription polymerase chain reaction in rat hypothalamus tissue and pancreatic islets cell. Results Expression of orexin mRNA increased about 150% in insulin induced hypoglycemia rat hypothalamus tissue, compared to control group ( P <0 01), whereas expression of OX 1R mRNA decreased up to 30% ( P <0 01). However, expression of OX 2R mRNA did not show significant change in comparison with control group. The expression of prepro orexin mRNA increased up to 100% in rat pancreas islet cell cultured in 1640 medium with 2 8 mmol/L glucose, compared to 8 3mmol/L glucose after 6 h ( P <0 01). But the expression of OX 1R mRNA level was not sensitive to acute glucose fluctuation. Conclusions The orexin and OX 1R are stimulated by falls in plasma glucose and inhibited by signals related to feeding. Moreover, glucose plays a role in modulating the gene expression of prepro orexin in rat pancreatic islet cells.