Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation.

dc.contributor.authorBorden, Philip
dc.contributor.authorHoutz, Jessica
dc.contributor.authorLeach, Steven D.
dc.contributor.authorKuruvilla, Rejji
dc.date.accessioned2014-04-04T15:09:53Z
dc.date.available2014-04-04T15:09:53Z
dc.date.issued2013-07-25
dc.descriptionPMC3740126en_US
dc.description.abstractSympathetic neurons depend on target-derived neurotrophic cues to control their survival and growth. However, whether sympathetic innervation contributes reciprocally to the development of target tissues is less clear. Here, we report that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation. Genetic or pharmacological ablation of sympathetic innervation during development resulted in altered islet architecture, reduced insulin secretion, and impaired glucose tolerance in mice. Similar defects were observed with pharmacological blockade of β-adrenergic signaling. Conversely, the administration of a β-adrenergic agonist restored islet morphology and glucose tolerance in deinnervated animals. Furthermore, in neuron-islet cocultures, sympathetic neurons promoted islet cell migration in a β-adrenergic-dependent manner. This study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders.en_US
dc.description.sponsorshipJH Libraries Open Access Funden_US
dc.identifier.citationdoi: 10.1016/j.celrep.2013.06.019en_US
dc.identifier.issn2211-1247
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/36748
dc.language.isoen_USen_US
dc.publisherCell Pressen_US
dc.relation.ispartofseriesCell Reports;v. 4 no. 2 p. 287 - 301
dc.subjectSympathetic Nervous Systemen_US
dc.subjectIslets of Langerhansen_US
dc.titleSympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation.en_US
dc.typeArticleen_US
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