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Here, we show that the parasympathetic nerve fibers and glial cells within and around the islets express GFR\u03b12 and that islet parasympathetic innervation in GFR\u03b12 knockout (KO) mice is reduced profoundly. In wild-type mice, neuroglucopenic stress produced a robust increase in plasma levels of islet hormones. In the GFR\u03b12-KO mice, however, pancreatic polypeptide and insulin responses were completely lost and glucagon response was markedly impaired. Islet morphology and sympathetic innervation, as well as basal secretions of the islet hormones, were unaffected. Moreover, a glucose tolerance test failed to reveal differences between the genotypes, indicating that direct glucose-stimulated insulin secretion was not affected by GFR\u03b12 deficiency. These results show that GFR\u03b12 signaling is needed for development of the parasympathetic islet innervation that is critical for vagally induced hormone secretion. The GFR\u03b12-KO mouse represents a useful model to study the role of parasympathetic innervation of the endocrine pancreas in glucose homeostasis.<\/jats:p>","DOI":"10.2337\/diabetes.54.5.1324","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1324-1330","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":48,"title":["Parasympathetic Innervation and Function of Endocrine Pancreas Requires the Glial Cell Line\u2013Derived Factor Family Receptor \u03b12 (GFR\u03b12)"],"prefix":"10.2337","volume":"54","author":[{"given":"Jari","family":"Rossi","sequence":"first","affiliation":[{"name":"Neuroscience Center, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paavo","family":"Santama\u0308ki","sequence":"additional","affiliation":[{"name":"Neuroscience Center, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti S.","family":"Airaksinen","sequence":"additional","affiliation":[{"name":"Neuroscience Center, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Herzig","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine, A.I. 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