Rezazadeh Hossein, Maghareh-Dehkordi Sajad, Touliat Mohammad Vahid, Talebi Ardeshir, Soltani Nepton
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Department of Biotechnology, Pharmacy and Pharmaceutical Sciences School, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2025 Aug 25;20(4):590-609. doi: 10.4103/RPS.RPS_94_24. eCollection 2025 Aug.
Diabetic nephropathy (DN) in the first and second generations of diabetic rats and improving kidney function by gamma aminobutyric acid (GABA) were investigated.
Male and female rats and their offspring were used. Diabetes was induced by a high-fat diet and a low dose of streptozotocin. Animals were divided into the diabetic positive control (D) group, the diabetic group receiving insulin (D + insulin), and the diabetic group receiving GABA (D + GABA). In addition, two groups of non-diabetic parents were assigned as negative control (NDC) groups. Each animal was monitored for 16 weeks, and offspring were fed with normal diet. The blood glucose level, urine volume, and water intake, as well as renal function, including the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and glomerular filtration rate (GFR) were assessed. Also, the hyperinsulinemic-euglycemic clamp and gene expressions of and in the kidneys were measured for all subjects.
FINDINGS/RESULTS: GABA administration in parents and offspring decreased blood glucose level, insulin resistance, GFR, serum levels of BUN and Cr compared to the D groups. GABA reduced the urine Cr, BUN, and albumin loads in both parents and offspring in comparison to the D groups. GABA decreased and gene expression in both parents and offspring.
GABA decreased the risk of DN, hyperglycemia, and insulin resistance in both diabetic parents and their offspring by improving kidney function, highlighting the potential therapeutic benefits of GABA in managing type 2 diabetes complications.
研究第一代和第二代糖尿病大鼠的糖尿病肾病(DN)以及γ-氨基丁酸(GABA)对肾功能的改善作用。
使用雄性和雌性大鼠及其后代。通过高脂饮食和低剂量链脲佐菌素诱导糖尿病。动物分为糖尿病阳性对照组(D组)、接受胰岛素的糖尿病组(D + 胰岛素组)和接受GABA的糖尿病组(D + GABA组)。此外,将两组非糖尿病亲代作为阴性对照组(NDC组)。对每只动物监测16周,后代喂食正常饮食。评估血糖水平、尿量和饮水量,以及肾功能,包括血清尿素氮(BUN)、肌酐(Cr)水平和肾小球滤过率(GFR)。同时,对所有受试者进行高胰岛素-正常血糖钳夹试验,并检测肾脏中相关基因的表达。
与D组相比,亲代和后代给予GABA后,血糖水平、胰岛素抵抗、GFR、血清BUN和Cr水平均降低。与D组相比,GABA降低了亲代和后代的尿Cr、BUN和白蛋白含量。GABA降低了亲代和后代中相关基因的表达。
GABA通过改善肾功能降低了糖尿病亲代及其后代患DN、高血糖和胰岛素抵抗的风险,突出了GABA在管理2型糖尿病并发症方面的潜在治疗益处。