title: The novel oral drug Subetta exerts an antidiabetic effect in the diabetic Goto-Kakizaki rat: comparison with rosiglitazone.
abstract: 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.
authors.affiliation: 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.
authors.forename: Danielle
authors.initials: D
authors.lastname: Bailbé
authors.forename: Erwann
authors.initials: E
authors.lastname: Philippe
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Gorbunov
authors.forename: Sergey
authors.initials: S
authors.lastname: Tarasov
authors.forename: Oleg
authors.initials: O
authors.lastname: Epstein
authors.forename: Bernard
authors.initials: B
authors.lastname: Portha
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D051381:Rats; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D052250:Nitric Oxide Synthase Type III; D011972:Receptor, Insulin