Catecholamines production by kidney tissue and mesangial cell culture is differentially modulated by diabetes

Abstract Introduction: According to the International Diabetes Federation, the number of people with diabetes mellitus may reach 700 million in 2045. Catecholamines are involved in the regulation of several kidney functions. This study investigates the effects of hyperglycemia on catecholamines' metabolism in kidney tissue from control, diabetic, and insulin-treated diabetic rats, both in vivo and in vitro. Methods: Male Wistar-Hannover rats were randomized into: control, diabetic, and insulin-treated diabetic groups. Diabetes was induced by a single injection of streptozotocin, and diabetic treated group also received insulin. After 60 days, blood and kidney tissue from all groups were collected for catecholamines' quantification and mesangial cells culture. Results: diabetic rats had lower body weight, hyperglycemia, and increase water intake and diuresis. Additionally, diabetes promoted a sharp decrease in creatinine clearance compared to control group. Regarding the whole kidney extracts, both diabetic groups (treated and non-treated) had significant reduction in norepinephrine concentration. In mesangial cell culture, catecholamines' concentration were lower in the culture medium than in the intracellular compartment for all groups. Norepinephrine, epinephrine, and dopamine medium levels were increased in the diabetic group. Conclusion: The major finding of the present study was that 8 weeks of diabetes induction altered the kidney catecholaminergic system in a very specific manner, once the production of catecholamines in the excised kidney tissue from diabetic rats was differentially modulated as compared with the production and secretion by cultured mesangial cells.

引言与摘要：据国际糖尿病联盟（International Diabetes Federation）统计，至2045年全球糖尿病患者数量或将达到7亿。儿茶酚胺（catecholamines）参与调控多项肾脏生理功能。本研究旨在探究高血糖对对照组、糖尿病模型组及胰岛素治疗组大鼠肾脏组织中儿茶酚胺代谢的影响，实验涵盖体内（in vivo）与体外（in vitro）两种研究模型。
方法：将雄性Wistar-Hannover大鼠随机分为对照组、糖尿病模型组与胰岛素治疗组。通过单次注射链脲佐菌素（streptozotocin）构建糖尿病模型，胰岛素治疗组同时予以胰岛素干预。造模60天后，采集各组大鼠血液与肾脏组织，用于儿茶酚胺定量检测及肾小球系膜细胞（mesangial cells）培养。
结果：糖尿病模型组大鼠体重低于对照组，呈现高血糖状态，饮水量与尿量均有所增加。此外，与对照组相比，糖尿病模型组大鼠的肌酐清除率显著下降。针对全肾提取物的检测结果显示，两个糖尿病组（治疗组与未治疗组）的去甲肾上腺素（norepinephrine）浓度均显著降低。在肾小球系膜细胞培养体系中，所有组别细胞培养液中的儿茶酚胺浓度均低于细胞内组分。糖尿病模型组的培养液中去甲肾上腺素、肾上腺素（epinephrine）与多巴胺（dopamine）水平均有所升高。
结论：本研究的核心发现为，造模8周的糖尿病大鼠肾脏儿茶酚胺能系统发生特异性改变——与培养的肾小球系膜细胞所产生并分泌的儿茶酚胺相比，糖尿病大鼠离体肾脏组织中儿茶酚胺的合成过程受到了差异化调控。