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Brevinin-2-related peptide and its [D4K] analogue stimulate insulin release in vitro and improve glucose tolerance in mice fed a high fat diet.

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Abdel-Wahab, Yasser, Patterson, Steven, Flatt, Peter and Conlon, M (2010) Brevinin-2-related peptide and its [D4K] analogue stimulate insulin release in vitro and improve glucose tolerance in mice fed a high fat diet. Hormone and Metabolic Research, 42(9) . pp. 652-656. [Journal article]

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Abstract

The cationic, alpha-helical frog skin antimicrobial peptide B2RP (brevinin-2-related peptide) shows sequence similarity to antimicrobial peptides belonging to the brevinin-2 family, but lacks the C-terminal cyclic heptapeptide domain (Cys-Lys-Xaa (4)-Cys). Synthetic B2RP produced a significant (p<0.05) stimulation of insulin release (148% of basal rate at a concentration of 1 muM with a maximum response of 222% of basal rate at a concentration of 3 muM) from BRIN-BD11 clonal beta-cells without increasing the release of the cytosolic enzyme, lactate dehydrogenase. Increasing cationicity of B2RP while maintaining amphipathicity by the substitution Asp (4) --> Lys enhanced the insulin-releasing potency (137% of basal rate at a concentration of 0.3 muM; p<0.05) with no stimulation of lactate dehydrogenase release. In contrast, the L18K, and D4K, L18K analogues were toxic to the cells, and the K16A analogue, with increased amphipathicity and hydrophobicity, showed reduced potency. Administration of [D4K]B2RP (100 nmol/kg body weight) to mice fed a high fat diet to induce obesity and insulin-resistance significantly (p<0.05) enhanced insulin release and improved glucose tolerance during the 60-minute period following an intraperitoneal glucose load (18 mmol/kg body weight). B2RP shows potential for development into an agent for the treatment of type 2 diabetes

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:14855
Deposited By:Dr Nigel Irwin
Deposited On:22 Sep 2010 12:10
Last Modified:22 Sep 2010 12:10

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