title: Antidiabetic efficacy of bradykinin antagonist R-954 on glucose tolerance test in diabetic type 1 mice.
abstract: Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with many complications including nephropathy, retinopathy, neuropathy and hyperalgesia. Experimental evidence has shown that the bradykinin B1 receptor (BKB1-R) is involved in the development of type 1 diabetes and found to be upregulated alongside the disease. In the present study the effects of the selective BKB1-R antagonist the R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8) ]des-Arg(9)-BK and the BKB1-R agonist des Arg(9)-BK (DBK) were studied on diabetic hyperglycemia. Diabetic type 1 was induced in C57 BL/KsJ mdb male mice by five consecutives doses of STZ (45mg/kg i.p.). A glucose tolerance test (GTT) was performed by an intraperitoneal administration of glucose, 8, 12 and 18days after the diabetes induction. The induction of type 1 diabetes provoked a significant hyperglycemia levels in diabetic mice at 12 and 18days after STZ. The administration of R-954 (400microg/kg i.p.) at 12 and 18days after STZ returned the glycemia levels of this animals to normal values. In addition the administration of DKB (300microg/kg i.p.) significantly potentiated the diabetes-induced hyperglycemia; this effect that was totally reversed by R-954. These results provide further evidence for the implication of BKB1-R in the type 1 diabetes mellitus (insulitis).
authors.affiliation: Direccion de Investigaciones Cientificas Bioquimico-Odontologicas, Universidad Argentina John F Kennedy, Argentina; Escuela de Medicina y Odontología, Universidad Del Salvador, Argentina. ocatan50@aol.com
authors.forename: Orlando L
authors.initials: OL
authors.lastname: Catanzaro
authors.forename: Damian
authors.initials: D
authors.lastname: Dziubecki
authors.forename: Pablo
authors.initials: P
authors.lastname: Obregon
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Rodriguez
authors.forename: Pierre
authors.initials: P
authors.lastname: Sirois
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice
chemical_list: C476306:Ac-Orn-(Oic2, alpha-MePhe5, D-betaNal7, Ile8)desArg9-bradykinin; D001786:Blood Glucose; D065169:Bradykinin B1 Receptor Antagonists; D001920:Bradykinin