Streptozotocin induction of diabetes in rats leads to increased insulin-like growth factor-II/mannose-6-phosphate receptor mRNA expression in kidney but not in lung or heart.

Growth regulation Pub Date : 1996-06-01
W Kiess, A Hoeflich, Y Yang, H Groenbaek, A Flyvbjerg
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Abstract

Insulin and glucose are thought to act as important modulators of the expression of the IGFs, their binding proteins and their receptors. It has been postulated that changes of the IGF system after diabetes onset contribute to the development of diabetes late complications. We have measured the expression of IGF-II/M6P receptor mRNA in rat kidney, lung and heart after streptozotocin induction of diabetes. Adult rats were injected with streptozotocin, and, after the onset of diabetes, were treated with either insulin or vehicle. The rats were sacrificed on days 1, 2, 3, 4 and 9. Kidneys, lungs and hearts were removed aseptically and RNA was extracted from the tissues. In solution hybridization/RNAse protection experiments, specific IGF-II/M6P receptor and beta-actin transcripts were detected in the RNA samples from all tissues examined. To gain additional evidence for the expression of IGF-II/M6P receptor RNA in the tissues examined, Northern blotting experiments were performed: a major 9 kb RNA species was detected on the blots. Interestingly, streptozotocin-induced onset of diabetes led to a significant increase in the expression of IGF-II/M6P receptor mRNA in the kidney but not in lung and heart whereas no change in actin mRNA expression was measured. Insulin treatment did not prevent the increase of IGF-II/M6P receptor mRNA expression during short-term treatment (1-9 days). Alterations of the IGF system during diabetes onset might be of relevance for the development of early renal changes during the course of the disease.

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链脲佐菌素诱导大鼠糖尿病导致肾脏中胰岛素样生长因子- ii /甘露糖-6-磷酸受体mRNA表达增加,但在肺和心脏中没有。
胰岛素和葡萄糖被认为是igf及其结合蛋白和受体表达的重要调节剂。据推测,糖尿病发病后IGF系统的改变有助于糖尿病晚期并发症的发生。我们测定了链脲佐菌素诱导糖尿病大鼠肾脏、肺和心脏中IGF-II/M6P受体mRNA的表达。成年大鼠注射链脲佐菌素,在糖尿病发作后,用胰岛素或载药治疗。第1、2、3、4、9天处死大鼠。无菌摘除肾脏、肺和心脏,从组织中提取RNA。在溶液杂交/RNAse保护实验中,在所有组织的RNA样本中检测到特异性的IGF-II/M6P受体和β -肌动蛋白转录物。为了获得IGF-II/M6P受体RNA在检查组织中表达的额外证据,进行了Northern印迹实验:在印迹上检测到主要的9 kb RNA种。有趣的是,链脲佐菌素诱导的糖尿病发病导致肾脏中IGF-II/M6P受体mRNA的表达显著增加,而肺和心脏中没有,而肌动蛋白mRNA的表达没有变化。在短期治疗(1-9天)期间,胰岛素治疗并未阻止IGF-II/M6P受体mRNA表达的增加。糖尿病发病期间IGF系统的改变可能与疾病过程中早期肾脏改变的发展有关。
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