Magainin-AM2 improves glucose homeostasis and beta cell function in high-fat fed mice

• Published in: Biochimica et biophysica acta Vol. 1850; no. 1; pp. 80 - 87
• Main Authors: Ojo, O.O., Srinivasan, D.K., Owolabi, B.O., Conlon, J.M., Flatt, P.R., Abdel-Wahab, Y.H.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2015
• Subjects: Amino Acid Sequence; Amphibian peptide; Animals; Blood Glucose - metabolism; Body Weight - drug effects; Diet, High-Fat; Energy Intake - drug effects; Glucose - metabolism; Homeostasis - drug effects; Insulin - blood; Insulin - metabolism; Insulin-release; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Magainin-AM2; Magainins - administration & dosage; Magainins - pharmacology; Male; Mice; Molecular Sequence Data; Obesity; Organ Size - drug effects; Pancreas - drug effects; Pancreas - growth & development; Time Factors; Type 2 diabetes; Xenopus Proteins - administration & dosage; Xenopus Proteins - pharmacology; Type 2 diabetes; Obesity; Magainin-AM2; Amphibian peptide; Insulin-release
• ISSN: 0304-4165; 0006-3002; 1872-8006; 1878-2434
• DOI: 10.1016/j.bbagen.2014.10.011

Magainin-AM2, a previously described amphibian host-defense peptide, stimulates insulin- and glucagon-like peptide-1-release in vitro. This study investigated anti-diabetic effects of the peptide in mice with diet-induced obesity and glucose intolerance. Male National Institute of Health Swiss mice were maintained on a high-fat diet for 12-weeks prior to the daily treatment with magainin-AM2. Various indices of glucose tolerance were monitored together with insulin secretory responsiveness of islets at conclusion of study. Following twice daily treatment with magainin-AM2 for 15days, no significant difference in body weight and food intake was observed compared with saline-treated high fat control animals. However, non-fasting blood glucose was significantly (P<0.05) decreased while plasma insulin concentrations were significantly (P<0.05) increased. Oral and intraperitoneal glucose tolerance and insulin secretion following glucose administration via both routes were significantly (P<0.05) enhanced. The peptide significantly (P<0.001) improved insulin sensitivity as well as the beta cell responses of islets isolated from treated mice to a range of insulin secretagogues. Oxygen consumption, CO2 production, respiratory exchange ratio and energy expenditure were not significantly altered by sub-chronic administration of magainin-AM2 but a significant (P<0.05) reduction in fat deposition was observed. These results indicate that magainin-AM2 improves glucose tolerance, insulin sensitivity and islet beta cells secretory responsiveness in mice with obesity-diabetes. The activity of magainin-AM2 suggests the possibility of exploiting this peptide for treatment of type 2 diabetes. •Magainin-AM2 improved glucose tolerance in high-fat fed mice.•Magainin-AM2 enhanced insulin sensitivity.•Magainin-AM2 improved secretory function of islets isolated from treated mice.