{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:52:32Z","timestamp":1782921152831,"version":"3.54.5"},"reference-count":72,"publisher":"Walter de Gruyter GmbH","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The frog skin host-defense peptide tigerinin-1R stimulates insulin release<jats:italic>in vitro<\/jats:italic>and improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observations by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg<jats:sup>4<\/jats:sup>]tigerinin-1R in mice with diet-induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on K<jats:sub>ATP<\/jats:sub>and L-type Ca<jats:sup>2+<\/jats:sup>channels in BRIN-BD11 clonal \u03b2 cells. Non-fasting plasma glucose and glucagon concentrations were significantly (<jats:italic>p<\/jats:italic>&lt;0.05) decreased and plasma insulin increased by twice daily treatment with [Arg<jats:sup>4<\/jats:sup>]tigerinin-1R (75 nmol\/kg body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (<jats:italic>p<\/jats:italic>&lt;0.05) improved accompanied by enhanced secretion and action of insulin. The peptide blocked K<jats:sub>ATP<\/jats:sub>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 (<jats:italic>Abcc8, Kcnj11, Cacna1c<\/jats:italic>and<jats:italic>Slc2a2<\/jats:italic>) and in skeletal muscle involved with insulin action (<jats:italic>Insr, Irs1, Pdk1,<\/jats:italic><jats:italic>Pik3ca,<\/jats:italic>and<jats:italic>Slc2a4<\/jats:italic>). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes.<\/jats:p>","DOI":"10.1515\/hsz-2016-0120","type":"journal-article","created":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T11:43:08Z","timestamp":1457696588000},"page":"753-764","source":"Crossref","is-referenced-by-count":19,"title":["Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance"],"prefix":"10.1515","volume":"397","author":[{"given":"Opeolu O.","family":"Ojo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh K.","family":"Srinivasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bosede O.","family":"Owolabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"McGahon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Charlotte","family":"Moffett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim M.","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Michael","family":"Conlon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser H.A.","family":"Abdel-Wahab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref201","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00726-015-2107-x","article-title":"In vitro and in vivo insulinotropic properties of the multifunctional frog skin peptide hymenochirin-1B: a structure-activity study","volume":"48","year":"2016","journal-title":"Amino Acids"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1016\/S0021-9258(18)69163-X","article-title":"A cascade of tyrosine autophosphorylation in the beta-subunit activates the phosphotransferase of the insulin receptor","volume":"263","year":"1988","journal-title":"J. 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