Increase of ATP-sensitive potassium (K(ATP)) channels in the heart of type-1 diabetic rats.

Increase of ATP-sensitive potassium (K(ATP)) channels in the heart of type-1 diabetic rats.
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DOI:
10.1186/1475-2840-11-8
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发表时间:
2012-01-18
影响因子:
9.3
通讯作者:
Cheng J
Cheng J
中科院分区:
医学1区
文献类型:
--
作者:
Chen ZC;Cheng YZ;Chen LJ;Cheng KC;Li Y;Cheng J

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链脲佐菌素(STZ)-糖尿病大鼠心血管功能的损害已被提及在5天至3个月的诱导。ATP敏感性钾通道(KATP)表达于心肌细胞膜上。它对代谢波动高度敏感,并可能对心脏收缩力产生影响。本研究试图阐明糖尿病心脏KATP通道的变化。使用链脲佐菌素诱导的糖尿病大鼠和用高浓度葡萄糖(使用30 mM的D-葡萄糖浓度并培养细胞24小时)处理的新生大鼠心肌细胞,以检查高血糖对心脏功能和KATP通道表达的影响。研究发现KATP通道的表达与心脏紧张性功能障碍有关,我们通过Western印迹和北方印迹分析评估了KATP通道的表达水平。结果表明,二氮嗪能明显降低对照组的心率。采用北方印迹和Western印迹方法检测KATP通道基因的表达。心肌KATP通道的两个亚基(SUR 2A和kir6.2)在糖尿病大鼠和高糖处理的大鼠心肌细胞中均显示出显著降低。通过胰岛素或根皮苷纠正高血糖恢复了这些糖尿病大鼠心脏KATP的基因表达。STZ诱导的糖尿病大鼠心肌KATP通道mRNA和蛋白表达均降低。这种现象导致某些KATP通道药物的脱敏。
An impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (KATP) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac KATP channels in diabetic disorders. Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr) were used to examine the effect of hyperglycemia on cardiac function and the expression of KATP channels. KATP channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of KATP channels by Western blot and Northern blot analysis. The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of KATP channel. Two subunits of cardiac KATP channel (SUR2A and kir 6.2) were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac KATP in these diabetic rats. Both mRNA and protein expression of cardiac KATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some KATP channel drugs.
DOI: 10.2337/dc05-2470
发表时间: 2006-06-01
期刊: DIABETES CARE
影响因子: 16.2
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Eppens, Maike C.;Craig, Maria E.;Donaghue, Kim C.
通讯作者: Donaghue, Kim C.
DOI: 10.1590/s0100-879x2002000900010
发表时间: 2002-09-01
影响因子: 2.3
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De Angelis, K.;Schaan, B.D.;Irigoyen, M.C.
通讯作者: Irigoyen, M.C.
DOI: 10.1161/01.cir.0000055187.67365.81
发表时间: 2003-02-11
期刊: CIRCULATION
影响因子: 37.8
作者:
Suzuki, M;Saito, T;Nakaya, H
通讯作者: Nakaya, H
DOI: 10.1016/s0304-3940(99)00871-x
发表时间: 1999-12-31
影响因子: 2.5
作者:
Tong, YC;Chin, WT;Cheng, JT
通讯作者: Cheng, JT
DOI: 10.1046/j.1523-1755.2001.00469.x
发表时间: 2001-01-01
影响因子: 19.6
作者:
Iglesias-de la Cruz, MC;Ruiz-Torres, P;Rodríguez-Puyol, D
通讯作者: Rodríguez-Puyol, D