Effects of acute and chronic STZ-induced diabetes on clock gene expression and feeding in the gastrointestinal tract
Effects of acute and chronic STZ-induced diabetes on clock gene expression and feeding in the gastrointestinal tract
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DOI：
10.1007/s11010-009-0354-4
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发表时间：
2010-05-01
影响因子：
4.3
通讯作者：
Hoogerwerf, Willemijntje A.
中科院分区：
文献类型：
--
作者：
Bostwick, Jonathon;Nguyen, Diane;Hoogerwerf, Willemijntje A.
糖尿病可能改变外周器官内的时钟基因表达。然而，关于糖尿病对胃肠道分子钟的影响知之甚少。因此，我们研究了糖尿病对胃肠道时钟基因表达的影响。由于外周时钟基因表达强烈受食物摄入的驱动，我们还确定了STZ诱导的糖尿病对食物摄入模式的影响。使用实时聚合酶链反应评估了急性（1周）和慢性（12周）STZ诱导的糖尿病对C57 BL/6 J小鼠胃体、近端和远端结肠、肝脏、肾脏和肺中周期（per）基因的影响。使用自动喂食设备完成摄食量研究。per 2和per 3表达的节律性在所有器官中持续存在。然而，与注射载体的小鼠相比，注射STZ的小鼠的per 2和per 3表达在胃肠道内通常是时相延迟的，但在肾脏或肺内不是。在12周时，近端结肠中per 2的相位延迟最明显。糖尿病小鼠的食物摄入具有节律性，昼夜节律幅度大于对照小鼠。因此，STZ诱导的糖尿病差异改变外周PER表达。STZ诱导的糖尿病不会改变食物摄入的昼夜节律。在糖尿病小鼠模型中，生物钟基因表达的改变在那些与食物加工和代谢密切相关的器官中最为明显。
Diabetes may shift clock gene expression within peripheral organs. However, little is known about the effect of diabetes on the gastrointestinal molecular clock. We therefore investigated the effect of diabetes on gastrointestinal clock gene expression. As peripheral clock gene expression is strongly driven by food intake, we also determined the effect of STZ-induced diabetes on patterns of food intake. The effects of acute (1 week) and chronic (12 weeks) STZ-induced diabetes on period (per) genes in the stomach body, proximal and distal colon, liver, kidney, and lung of C57BL/6J mice were assessed using real-time polymerase chain reaction. Food intake studies were completed using automated feeding equipment. Rhythmicity in expression of per2 and per3 persisted in all organs. However, per2 and per3 expression of STZ-injected mice was generally phase delayed within the gastrointestinal tract but not within the kidney or lung as compared with vehicle-injected mice. The phase delay was most pronounced for per2 in the proximal colon at 12 weeks. Food intake was rhythmic with larger circadian amplitude for diabetic mice than for control mice. Thus, STZ-induced diabetes differentially alters peripheral per expression. STZ-induced diabetes does not alter the circadian phase of food intake. Alterations in clock gene expression in a mouse model of diabetes are most pronounced in those organs that are intimately associated with food processing and metabolism.