{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:31:43Z","timestamp":1784957503832,"version":"3.55.0"},"reference-count":38,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>\n                    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on \u03b2-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose\u00b1glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose\u00b1GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges\n                    <jats:italic>in vivo<\/jats:italic>\n                    and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased \u03b2-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of \u03b2-cell function during development of type 2 diabetes.\n                  <\/jats:p>","DOI":"10.1530\/joe-15-0371","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T22:48:37Z","timestamp":1450910917000},"page":"171-178","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":5,"title":["Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice"],"prefix":"10.1530","volume":"228","author":[{"given":"Linda","family":"Ahlkvist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Omar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Valeur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keld","family":"Fosgerau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Ahr\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2016021719334570000_228.3.171.1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-12-0079"},{"key":"2016021719334570000_228.3.171.2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1615"},{"key":"2016021719334570000_228.3.171.3","first-page":"283","article-title":"Endocrine manipulation of body composition in broiler chickens","volume":"3","author":"Cogburn","year":"1991","journal-title":"Critical Reviews in Poultry Biology"},{"key":"2016021719334570000_228.3.171.4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.27.19455"},{"key":"2016021719334570000_228.3.171.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.10.3434"},{"key":"2016021719334570000_228.3.171.6","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0140-6736(73)91605-X","article-title":"Glucagon resistance as a hormonal basis for endogenous hyperlipaemia","volume":"1","author":"Eaton","year":"1973","journal-title":"Lancet"},{"key":"2016021719334570000_228.3.171.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2013.11.019"},{"key":"2016021719334570000_228.3.171.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2005.03.024"},{"key":"2016021719334570000_228.3.171.9","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051484"},{"key":"2016021719334570000_228.3.171.10","doi-asserted-by":"publisher","DOI":"10.1007\/BF00400630"},{"key":"2016021719334570000_228.3.171.11","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.5.650"},{"key":"2016021719334570000_228.3.171.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3518-7"},{"key":"2016021719334570000_228.3.171.13","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0251"},{"key":"2016021719334570000_228.3.171.14","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3115"},{"key":"2016021719334570000_228.3.171.15","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.2.257"},{"key":"2016021719334570000_228.3.171.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(96)00071-9"},{"key":"2016021719334570000_228.3.171.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.09.004"},{"key":"2016021719334570000_228.3.171.18","doi-asserted-by":"publisher","DOI":"10.3382\/ps.0751027"},{"key":"2016021719334570000_228.3.171.19","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-66-6-1220"},{"key":"2016021719334570000_228.3.171.20","doi-asserted-by":"publisher","DOI":"10.1210\/endo-117-3-824"},{"key":"2016021719334570000_228.3.171.21","doi-asserted-by":"crossref","first-page":"16087","DOI":"10.1016\/S0021-9258(18)37562-8","article-title":"Glucagon-induced desensitization of adenylyl cyclase in primary cultures of chick hepatocytes. Evidence for multiple pathways","volume":"263","author":"Premont","year":"1988","journal-title":"Journal of Biological Chemistry"},{"key":"2016021719334570000_228.3.171.22","doi-asserted-by":"publisher","DOI":"10.2337\/db13-388-679"},{"key":"2016021719334570000_228.3.171.23","doi-asserted-by":"publisher","DOI":"10.2337\/db14-389-664"},{"key":"2016021719334570000_228.3.171.24","doi-asserted-by":"publisher","DOI":"10.2337\/db10-1032"},{"key":"2016021719334570000_228.3.171.25","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/BF00279918","article-title":"Production of insulin resistance by hyperinsulinaemia in man","volume":"28","author":"Rizza","year":"1985","journal-title":"Diabetologia"},{"key":"2016021719334570000_228.3.171.26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107251"},{"key":"2016021719334570000_228.3.171.27","doi-asserted-by":"publisher","DOI":"10.2337\/diab.15.12.855"},{"key":"2016021719334570000_228.3.171.28","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/j.1432-1033.1982.tb05838.x","article-title":"Direct evidence of a glucagon-dependent regulation of the concentration of glucagon receptors in the liver","volume":"121","author":"Santos","year":"1982","journal-title":"European Journal of Biochemistry"},{"key":"2016021719334570000_228.3.171.29","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/BF00253583","article-title":"Regulatory effect of glucagon on its own receptor concentrations and target-cell sensitivity in the rat","volume":"22","author":"Santos","year":"1982","journal-title":"Diabetologia"},{"key":"2016021719334570000_228.3.171.30","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(77)90127-5"},{"key":"2016021719334570000_228.3.171.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.005"},{"key":"2016021719334570000_228.3.171.32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.271be.x"},{"key":"2016021719334570000_228.3.171.33","doi-asserted-by":"publisher","DOI":"10.2337\/diab.13.6.563"},{"key":"2016021719334570000_228.3.171.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)18841-0"},{"key":"2016021719334570000_228.3.171.35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01116.x"},{"key":"2016021719334570000_228.3.171.36","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.2.398"},{"key":"2016021719334570000_228.3.171.37","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.suppl_3.S215"},{"key":"2016021719334570000_228.3.171.38","doi-asserted-by":"publisher","DOI":"10.1177\/1535370214524877"}],"container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/228\/3\/171.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/228\/3\/171.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:09Z","timestamp":1784555709000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/228\/3\/171-178\/22817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,23]]},"references-count":38,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/joe-15-0371","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,23]]}}}