Laboratoire B2PE (Biologie et Pathologie du Pancréas Endocrine), Unité BFA (Biologie Fonctionnelle et Adaptive), Equipe 1, Université Paris-Diderot et CNRS EAC 4413, 4 rue Lagroua Weill Hallé, Paris Cedex 13, France.
J Diabetes Res. 2013;2013:763125. doi: 10.1155/2013/763125. Epub 2013 May 8.
The aim of the present study was to evaluate the potential antidiabetic effects of two-component drug Subetta and its components (release-active dilutions of antibodies to β -subunit insulin receptor (RAD of Abs to β -InsR) and to endothelial nitric oxide synthase (RAD of Abs to eNOS)) in Goto-Kakizaki (Paris colony) (GK/Par) diabetic rats. Subetta was administered orally for 28 days once daily (5 mL/kg) and compared to its two components (2.5 mL/kg), Rosiglitazone (5 mg/kg), and vehicle (5 mL water/kg). At day 28, fasting plasma glucose levels were significantly decreased only in Subetta and Rosiglitazone groups as compared to vehicle (P < 0.01): 147 ± 4 mg/dL and 145 ± 4 mg/dL and 165 ± 4 mg/dL, respectively. The data of glucose tolerance test showed that Subetta and RAD of Abs to β -InsR (similar to Rosiglitazone) prevented significantly (P < 0.01) the age-related spontaneous deterioration of glucose tolerance as seen in the control group. Subetta and RAD of Abs to β -InsR did not significantly modify the glucose-induced insulin secretion. Chronic administration of Subetta and RAD of Abs to β -InsR improves glucose control, to an extent similar to that of Rosiglitazone. We hypothesize that Subetta and RAD of Abs to β -InsR mostly act via an insulin-sensitizing effect upon target tissues.
本研究旨在评估双组分药物 Subetta 及其成分(针对β-亚单位胰岛素受体的释放活性稀释抗体 (RAD of Abs to β -InsR) 和内皮型一氧化氮合酶 (RAD of Abs to eNOS))在 Goto-Kakizaki(巴黎群体)(GK/Par)糖尿病大鼠中的潜在抗糖尿病作用。Subetta 每天口服一次,持续 28 天(5 mL/kg),并与两种成分(2.5 mL/kg)、罗格列酮(5 mg/kg)和载体(5 mL/kg 水)进行比较。第 28 天,与载体相比,仅 Subetta 和罗格列酮组的空腹血糖水平显著降低(P < 0.01):分别为 147 ± 4 mg/dL 和 145 ± 4 mg/dL 和 165 ± 4 mg/dL。葡萄糖耐量试验结果表明,Subetta 和 RAD of Abs to β -InsR(与罗格列酮相似)可显著预防对照组中与年龄相关的葡萄糖耐量自发性恶化(P < 0.01)。Subetta 和 RAD of Abs to β -InsR 对葡萄糖诱导的胰岛素分泌没有显著影响。Subetta 和 RAD of Abs to β -InsR 的慢性给药可改善血糖控制,其程度与罗格列酮相似。我们假设 Subetta 和 RAD of Abs to β -InsR 主要通过对靶组织的胰岛素增敏作用发挥作用。