Tolbutamide alters glucose transport and metabolism in the embryonic mouse heart.
Tolbutamide alters glucose transport and metabolism in the embryonic mouse heart.
复制标题
甲苯磺丁脲改变胚胎小鼠心脏中的葡萄糖转运和代谢。
DOI：
10.1002/tera.1094
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Smoak,IdaW
中科院分区：
文献类型：
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作者：
Smoak,IdaW
背景甲苯磺丁脲是一种磺脲类口服降糖药，广泛用于治疗非胰岛素依赖型糖尿病。甲苯磺丁脲在啮齿动物胚胎中产生畸形，并在母体口服给药后集中在胚胎心脏中。甲苯磺丁脲增加葡萄糖代谢的胰腺外成人组织，但这还没有以前被检查在胚胎heart.MethodsCD-1小鼠胚胎暴露于GD 9.5甲苯磺丁脲（0，100，250，或500 μ g/ml）为6，12，或24小时的全胚胎培养。评价离体心脏的3H-2DG摄取和14 C-葡萄糖向14 C-乳酸的转化。Glut-1，HKI和GRP78蛋白水平通过Western分析测定，Glut-1 mRNA通过RT-PCR测定。结果与对照组相比，暴露于500 μ g/ml甲苯磺丁脲6 h和100、250或500 μ g/ml甲苯磺丁脲24 h后，心脏3H-2DG摄取增加。与对照组相比，暴露于500 μ g/ml甲苯磺丁脲6或24小时后，糖酵解增加。与对照组相比，暴露于500 μ g/ml甲苯磺丁脲12或24小时的心脏中Glut-1蛋白水平增加，暴露于500 μ g/ml甲苯磺丁脲24小时的心脏中Glut-1 mRNA增加。HKI蛋白水平增加心脏暴露于500 μ g/ml甲苯磺丁脲为6小时，但不是12或24 hr.There是没有影响GRP78蛋白水平暴露于甲苯磺丁脲为6，12，或24 hr.ConclusionsTolbutamide刺激葡萄糖摄取和代谢在胚胎心脏中，发生在成人胰腺外组织。Glut-1和HKI，而不是GRP78，可能参与甲苯磺丁脲诱导的心脏畸形。畸形学65：19 - 25，2002年。© 2002 Wiley利斯公司
BackgroundTolbutamide is a sulfonylurea oral hypoglycemic agent widely used for the treatment of non insulin‐dependent diabetes mellitus. Tolbutamide produces dysmorphogenesis in rodent embryos and becomes concentrated in the embryonic heart after maternal oral dosing. Tolbutamide increases glucose metabolism in extra‐pancreatic adult tissues, but this has not previously been examined in embryonic heart.MethodsCD‐1 mouse embryos were exposed on GD 9.5 to tolbutamide (0, 100, 250, or 500 μg/ml) for 6, 12, or 24 hr in whole‐embryo culture. Isolated hearts were evaluated for3H‐2DG uptake and conversion of14C‐glucose to14C‐lactate. Glut‐1, HKI, and GRP78 protein levels were determined by Western analysis, and Glut‐1 mRNA was measured by RT‐PCR.ResultsCardiac3H‐2DG uptake increased after exposure to 500 μg/ml tolbutamide for 6 hr, and 100, 250, or 500 μg/ml tolbutamide for 24 hr, compared to controls. Glycolysis increased after exposure to 500 μg/ml tolbutamide for 6 or 24 hr compared to controls. Glut‐1 protein levels increased in hearts exposed to 500 μg/ml tolbutamide for 12 or 24 hr, and Glut‐1 mRNA increased in hearts exposed to 500 μg/ml tolbutamide for 24 hr compared to controls. HKI protein levels increased in hearts exposed to 500 μg/ml tolbutamide for 6 hr, but not 12 or 24 hr. There was no effect on GRP78 protein levels in hearts exposed to tolbutamide for 6, 12, or 24 hr.ConclusionsTolbutamide stimulates glucose uptake and metabolism in the embryonic heart, as occurs in adult extra‐pancreatic tissues. Glut‐1 and HKI, but not GRP78, are likely involved in tolbutamide‐induced cardiac dysmorphogenesis. Teratology 65:19–25, 2002. © 2002 Wiley‐Liss, Inc.