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Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance

Ojo, OO, Srinivasan, DK, Owolabi, BO, McGahon, MK, Moffett, Charlotte, Curtis, TM, Conlon, JM, Flatt, Peter and Abdel-Wahab, Yasser (2016) Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance. Biological Chemistry, 397 (8). pp. 753-764. [Journal article]

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DOI: 10.1515/hsz-2016-0120

Abstract

The frog skin host-defense peptide tigerinin-1R stimulates insulin release in vitro and improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observation by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg4]tigerinin-1R in mice with diet induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on KATP and L-type Ca2+ channels in BRINBD11 clonal β cells. Non-fasting plasma glucose and glucagon concentrations were significantly (P<0.05) decreased and plasma insulin increased by twice daily treatment with [Arg4]tigerinin-1R (75 nmol.kg-1 body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (P < 0.05) improved accompanied by enhanced secretion and action of insulin. The peptide blocked KATP channels and, consistent with this, improved beta cell responses of isolated islets to a range of secretagogues. Peptide administration resulted in up-regulation of key functional genes in islets involved insulin secretion (Abcc8, Kcnj11, Cacna1c and Slc2a2) and in skeletal muscle involved with insulin action (Insr, Irs1, Pdk1, Pik3ca, and Slc2a4). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes

Item Type:Journal article
Keywords:tigerinin-1R; insulin resistance; high fat feeding, insulin secretion, antihyperglycaemic
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:34515
Deposited By: Dr Nigel Irwin
Deposited On:26 Apr 2016 09:26
Last Modified:01 Jun 2017 14:30

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