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Insulin-releasing and cytotoxic properties of the frog skin peptide, tigerinin-1R: a structure-activity study

Srinivasan, D, Ojo, Opeolu, Abdel-Wahab, Yasser, Flatt, Peter, Guilhaudis, L and Conlon, JM (2014) Insulin-releasing and cytotoxic properties of the frog skin peptide, tigerinin-1R: a structure-activity study. Peptides, 55 . pp. 23-31. [Journal article]

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insulin release and cytotoxicity of changes in cationicity and hydrophobicity produced by selected substitutions of amino acids by l-arginine, l-lysine and l-tryptophan. The [A5W], [L8W] and [I10W] analogs produced a significant (P<0.01) increase in the rate of insulin release from BRIN-BD11 rat clonal β cells at concentration of 0.01nM compared with 0.1nM for tigerinin-1R. The increase in the rate of insulin release produced by a 3μM concentration of the [S4R], [H12K], and [I10W] analogs from both BRIN-BD11 cells and mouse islets was significantly greater (P<0.05) than that produced by tigerinin-1R. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3μM indicating that plasma membrane integrity had been preserved. [A5W] tigerinin-1R was the only analog tested that showed cytotoxic activity against human erythrocytes (LC50=265±16μM) and inhibited growth of Escherichia coli (MIC=500μM) and Staphylococcus aureus (MIC=250μM). The circular dichroism spectra of tigerinin-1R and [A5W] tigerinin-1R indicate that the peptides adopt a mixture of β-sheet, random coil and reverse β-turn conformations in 50% trifluoroethanol/water and methanol/water. Administration of [S4R] tigerinin-1R (75nmol/kg body weight) to high-fat fed mice with insulin resistance significantly (P<0.05) enhanced insulin release and improved glucose tolerance over a 60min period following an intraperitoneal glucose load. The study supports the claim that tigerinin-1R shows potential for development into novel therapeutic agents for treatment of type 2 diabetes mellitus.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:29318
Deposited By: Dr Nigel Irwin
Deposited On:28 Apr 2014 08:45
Last Modified:28 Apr 2014 08:45

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