{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:58:48Z","timestamp":1776275928584,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,8,19]],"date-time":"2014-08-19T00:00:00Z","timestamp":1408406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Invest NI Proof of Concept funding","award":["POC106"],"award-info":[{"award-number":["POC106"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To examine the effect of two novel, enzymatically stable, glucagon receptor peptide antagonists, on metabolic control in two mouse models of obesity\/diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      The effects of twice daily i.p. administration of\n                      <jats:styled-content style=\"fixed-case\">\n                        desHis\n                        <jats:sup>1<\/jats:sup>\n                        Pro\n                        <jats:sup>4<\/jats:sup>\n                        Glu\n                        <jats:sup>9<\/jats:sup>\n                      <\/jats:styled-content>\n                      \u2010glucagon or\n                      <jats:styled-content style=\"fixed-case\">\n                        desHis\n                        <jats:sup>1<\/jats:sup>\n                        Pro\n                        <jats:sup>4<\/jats:sup>\n                        Glu\n                        <jats:sup>9<\/jats:sup>\n                        Lys\n                        <jats:sup>12<\/jats:sup>\n                        FA\n                      <\/jats:styled-content>\n                      \u2010glucagon for 10 days on metabolic control in high\u2010fat\u2010fed (\n                      <jats:styled-content style=\"fixed-case\">HFF<\/jats:styled-content>\n                      ; 45% fat) and obese diabetic (\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      ) mice were compared with saline\u2010treated controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Neither analogue altered body weight or food intake in either model over 10 days; however, treatment with each peptide restored non\u2010fasting blood glucose towards normal control values in\n                      <jats:styled-content style=\"fixed-case\">HFF<\/jats:styled-content>\n                      mice. Basal glucose was also reduced (p &lt; 0.01) in\n                      <jats:styled-content style=\"fixed-case\">\n                        desHis\n                        <jats:sup>1<\/jats:sup>\n                        Pro\n                        <jats:sup>4<\/jats:sup>\n                        Glu\n                        <jats:sup>9<\/jats:sup>\n                        Lys\n                        <jats:sup>12<\/jats:sup>\n                        FA\n                      <\/jats:styled-content>\n                      \u2010glucagon treated\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice by day 10, coinciding with increases (p &lt; 0.001) in circulating insulin. At the end of the treatment period, both analogues significantly (p &lt; 0.05\u20130.01) improved oral and i.p. glucose tolerance (p &lt; 0.05) and peripheral insulin sensitivity, increased pancreatic insulin and glucagon content (p &lt; 0.05\u20130.01) and decreased (p &lt; 0.05) cholesterol levels in\n                      <jats:styled-content style=\"fixed-case\">HFF<\/jats:styled-content>\n                      mice. Similarly beneficial metabolic effects on oral glucose tolerance (p &lt; 0.01) and pancreatic insulin content (p &lt; 0.05) were observed in\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice, especially after\n                      <jats:styled-content style=\"fixed-case\">\n                        desHis\n                        <jats:sup>1<\/jats:sup>\n                        Pro\n                        <jats:sup>4<\/jats:sup>\n                        Glu\n                        <jats:sup>9<\/jats:sup>\n                        Lys\n                        <jats:sup>12<\/jats:sup>\n                        FA\n                      <\/jats:styled-content>\n                      \u2010glucagon treatment. No significant differences in circulating triglycerides or aspects of indirect calorimetry were noted between peptide treatment groups and respective control\n                      <jats:styled-content style=\"fixed-case\">HFF<\/jats:styled-content>\n                      and\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice. Finally, glucagon\u2010mediated elevations of glucose and insulin were significantly (p &lt; 0.05\u20130.01) annulled after 10 days of\n                      <jats:styled-content style=\"fixed-case\">\n                        desHis\n                        <jats:sup>1<\/jats:sup>\n                        Pro\n                        <jats:sup>4<\/jats:sup>\n                        Glu\n                        <jats:sup>9<\/jats:sup>\n                      <\/jats:styled-content>\n                      \u2010glucagon or\n                      <jats:styled-content style=\"fixed-case\">\n                        desHis\n                        <jats:sup>1<\/jats:sup>\n                        Pro\n                        <jats:sup>4<\/jats:sup>\n                        Glu\n                        <jats:sup>9<\/jats:sup>\n                        Lys\n                        <jats:sup>12<\/jats:sup>\n                        FA\n                      <\/jats:styled-content>\n                      \u2010glucagon treatment in both animal models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data indicate that peptide\u2010based glucagon receptor antagonists can reverse aspects of genetically and dietary\u2010induced obesity\u2010related diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12360","type":"journal-article","created":{"date-parts":[[2014,7,25]],"date-time":"2014-07-25T05:12:07Z","timestamp":1406265127000},"page":"1214-1222","source":"Crossref","is-referenced-by-count":24,"title":["Two novel glucagon receptor antagonists prove effective therapeutic agents in high\u2010fat\u2010fed and obese diabetic mice"],"prefix":"10.1111","volume":"16","author":[{"given":"F. 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