{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:34:27Z","timestamp":1792204467387,"version":"4.4.0"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"3","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,2,4]]},"abstract":"<jats:p>\n                    Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic \u03b1 cells in response to low blood glucose. To examine the role of glucagon in glucose homeostasis, mice were generated with a null mutation of the glucagon receptor (Gcgr\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ). These mice display lower blood glucose levels throughout the day and improved glucose tolerance but similar insulin levels compared with control animals. Gcgr\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice displayed supraphysiological glucagon levels associated with postnatal enlargement of the pancreas and hyperplasia of islets due predominantly to \u03b1 cell, and to a lesser extent, \u03b4 cell proliferation. In addition, increased proglucagon expression and processing resulted in increased pancreatic glucogen-like peptide 1 (GLP-1) (1\u201337) and GLP-1 amide (1\u201336 amide) content and a 3- to 10-fold increase in circulating GLP-1 amide. Gcgr\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice also displayed reduced adiposity and leptin levels but normal body weight, food intake, and energy expenditure. These data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and \u03b1 and \u03b4 cell numbers. Furthermore, the lean phenotype of Gcgr\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice suggests glucagon action may be involved in the regulation of whole body composition.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0237106100","type":"journal-article","created":{"date-parts":[[2003,2,4]],"date-time":"2003-02-04T12:24:41Z","timestamp":1044361481000},"page":"1438-1443","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":521,"title":["Lower blood glucose, hyperglucagonemia, and pancreatic \u03b1 cell hyperplasia in glucagon receptor knockout mice"],"prefix":"10.1073","volume":"100","author":[{"given":"R. W.","family":"Gelling","sequence":"first","affiliation":[{"name":"Departments of Diabetes Biology, Pharmacological Research 4, Pharmacological Research 2, and Pharmacological Research 3, Novo Nordisk A\/S, DK-2880 Bagsvaerd, Denmark; Departments of Biochemistry, Medicine (Endocrinology), and Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Developmental Biology, Hagedorn Research Institute, DK-2820 Gentofte, Denmark; and Department of Medical Physiology, Panum Institute, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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