Obineche Enyioma N, Adeghate Ernest, Chandranath Irwin S, Benedict Sheela, Al Gafri Laila S, Adem Abdu
Departments of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
Mol Cell Biochem. 2004 Jun;261(1-2):3-8. doi: 10.1023/b:mcbi.0000028732.15710.c2.
In this study the effect of diabetes mellitus on atrial natriuretic peptide (ANP) receptors in streptozotocin- (STZ-) induced diabetic rat kidneys was studied. Moreover, plasma ANP concentration was evaluated in diabetic and control rats by using radioimmunoassay. In addition, the expression of ANP in the kidneys of control and diabetic rats was evaluated by immunohistochemistry. Body-weight loss and increased glucose levels were used as indices of diabetes mellitus in the STZ-induced rats. There was a significant loss in the body weight of the diabetic rats compared to controls. The efficacy of STZ administration was confirmed by rising blood glucose levels, which were significantly higher in diabetic rats compared to controls. Plasma ANP concentration was significantly greater in the diabetic rats in comparison with controls. Moreover, our immunohistochemical results show that the expression of ANP in diabetic rats was higher than that in age-matched controls. ANP was observed in the cells lining the proximal convoluted tubules in the cortex. The distribution and levels of ANP receptors in the kidneys of diabetic rats and age-matched controls were investigated using quantitative receptor autoradiography. Our results demonstrate significant decrease in ANP receptors in the kidneys of the diabetic rats compared to controls. The significant decrease was found in the juxtaglomerular medulla, inner medulla, and the papillae. The decrease in ANP receptors observed in the diabetic kidneys could have pathological consequences resulting in renal resistance to ANP in diabetes.
在本研究中,我们研究了糖尿病对链脲佐菌素(STZ)诱导的糖尿病大鼠肾脏中利钠肽(ANP)受体的影响。此外,通过放射免疫分析法评估了糖尿病大鼠和对照大鼠的血浆ANP浓度。另外,采用免疫组织化学法评估了对照大鼠和糖尿病大鼠肾脏中ANP的表达。体重减轻和血糖水平升高被用作STZ诱导大鼠患糖尿病的指标。与对照组相比,糖尿病大鼠体重显著减轻。通过血糖水平升高证实了STZ给药的效果,糖尿病大鼠的血糖水平显著高于对照组。与对照组相比,糖尿病大鼠的血浆ANP浓度显著更高。此外,我们的免疫组织化学结果显示,糖尿病大鼠中ANP的表达高于年龄匹配的对照组。在皮质近曲小管的内衬细胞中观察到了ANP。使用定量受体放射自显影术研究了糖尿病大鼠和年龄匹配的对照大鼠肾脏中ANP受体的分布和水平。我们的结果表明,与对照组相比,糖尿病大鼠肾脏中的ANP受体显著减少。在肾小球旁髓质、内髓质和乳头中发现了显著减少。糖尿病肾脏中观察到的ANP受体减少可能会导致病理后果,从而导致糖尿病时肾脏对ANP产生抵抗。