Magainin-Related Peptides Stimulate Insulin-Release and Improve Glucose Tolerance in High Fat Fed Mice

Author(s): Opeolu Oyejide Ojo, Dinesh Kumar Srinivasan, Bosede Olayinka Owolabi, Peter Raymond Flatt, Yasser Hassan Atef Abdel-Wahab.

Journal Name: Protein & Peptide Letters

Volume 22 , Issue 3 , 2015

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Abstract:

Earlier peptidomic analysis of the skin secretion of Xenopus amieti led to the identification of orthologs of magainins and other peptides. This study investigated the degradation, in vitro insulin-releasing and acute metabolic effects of magainin-AM1 (GIKEFAHSLGKFG KAFVGGILNQ) and magainin–AM2 (GVSKILHSAGKFGKAFLGEIMKS). Plasma degradation was investigated using reversed-phase HPLC and MALDI-TOF mass spectroscopy. Insulin-releasing effects were determined using BRIN-BD11 clonal beta cells and mouse islets. Effects of magainin peptides on cytosolic enzyme lactate dehydrogenase release, membrane potential and intracellular Ca2+ concentration were assessed using BRIN-BD11 cells while their in vivo effects on glucose tolerance and insulin release were assessed in obese, insulin-resistant Swiss National Institute of Health (NIH) mice. Both peptides were resistant to degradation by plasma enzymes in vitro for up to 8 h. Though magainin-AM1 elicited non-toxic, concentration-dependent stimulation of insulin-release from clonal BRINBD11 cells at concentrations ≥ 100nM, magainin-AM2 produced a higher stimulation of insulin-release from BRIN-BD11 cells and isolated mouse islets. Membrane depolarization and intracellular [Ca2+]i in BRIN-BD11 cells were significantly (P<0.05) induced by both peptides and chelation of extracellular Ca2+, addition of diazoxide or verapamil significantly (P<0.01) reduced the insulinotropic actions of the peptides. Administration of magainin-AM2 (75 nmol/kg body weight) to high-fat fed mice significantly enhanced insulin-release (P<0.01) and improved glucose tolerance (P<0.05). These data indicate magainin-AM2 peptides have potential for development into agents for treatment of type 2 diabetes.

Keywords: Glucose tolerance, high fat-fed mice, host-defence peptides, insulin-release, magainin.

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Article Details

VOLUME: 22
ISSUE: 3
Year: 2015
Page: [256 - 263]
Pages: 8
DOI: 10.2174/0929866521666141229105757
Price: $58

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