{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:52:04Z","timestamp":1792115524679,"version":"4.4.0"},"reference-count":36,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3144,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:p>Glucagon and glucagon-like peptide-1 (GLP-1) are produced in pancreatic \u03b1-cells and enteroendocrine L-cells, respectively, in a tissue-specific manner from the same precursor, proglucagon, that is encoded by glucagon gene (Gcg), and play critical roles in glucose homeostasis. Here, we studied glucose homeostasis and \u03b2-cell function of Gcg-deficient mice that are homozygous for a Gcg-GFP knock-in allele (Gcggfp\/gfp). The Gcggfp\/gfp mice displayed improved glucose tolerance and enhanced insulin secretion, as assessed by both oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT). Responses of glucose-dependent insulinotropic polypeptide (GIP) to both oral and intraperitoneal glucose loads were unexpectedly enhanced in Gcggfp\/gfp mice, and immunohistochemistry localized GIP to pancreatic \u03b2-cells of Gcggfp\/gfp mice. Furthermore, secretion of GIP in response to glucose was detected in isolated islets of Gcggfp\/gfp mice. Blockade of GIP action in vitro and in vivo by cAMP antagonism and genetic deletion of the GIP receptor, respectively, almost completely abrogated enhanced insulin secretion in Gcggfp\/gfp mice. These results indicate that ectopic GIP expression in \u03b2-cells maintains insulin secretion in the absence of proglucagon-derived peptides (PGDPs), revealing a novel compensatory mechanism for sustaining incretin hormone action in islets.<\/jats:p>","DOI":"10.2337\/db12-0294","type":"journal-article","created":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T17:35:56Z","timestamp":1351791356000},"page":"510-518","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":27,"title":["Ectopic Expression of GIP in Pancreatic \u03b2-Cells Maintains Enhanced Insulin Secretion in Mice With Complete Absence of Proglucagon-Derived Peptides"],"prefix":"10.2337","volume":"62","author":[{"given":"Ayako","family":"Fukami","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Seino","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan"},{"name":"Department of Metabolic Medicine, Nagoya University School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan"},{"name":"Research Center of Health, Physical Fitness, and Sports, Nagoya University, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiyo","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Genetics, Division of Stress Adaptation and Recognition, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Genetics, Division of Stress Adaptation and Recognition, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Sakamoto-Miura","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhito","family":"Himeno","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Takagishi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Division of Stress Adaptation and Recognition, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Tsunekawa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safina","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Drucker","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiharu","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Genetics, Division of Stress Adaptation and Recognition, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Seino","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Clinical Nutrition, and Endocrinology, Department of Medicine, Kansai Electric Power Hospital, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Oiso","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Division of Stress Adaptation 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