Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice

Jung Dae Kim; Chitoku Toda; Giuseppe DAgostinoCaroline J. ZeissRalph J. DiLeoneJohn D. ElsworthRichard G. KibbeyOwen ChanBrandon K. HarveyChristopher T. RichieMari SavolainenTimo My?h?nenJin Kwon JeongSabrina Diano

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice

【24h】

Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice

机译：Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report that hypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP knockdown mice (Prep~(gt/gt)) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulin secretion compared with wild-type controls. Consistent with this, central infusion of a specific PREP inhibitor, S17092, impaired glucose tolerance and decreased insulin levels in wild-type mice. Arguing further for a central mode of action of PREP, isolated pancreatic islets showed no difference in glucose-induced insulin release between Prep~(gt/gt) and wild-type mice. Furthermore, hyperinsulinemic euglycemic clamp studies showed no difference between Prep~(gt/gt) and wild-type control mice. Central PREP regulation of insulin and glucagon secretion appears to be mediated by the autonomic nervous system because Prep~(gt/gt) mice have elevated sympathetic outflow and norepinephrine levels in the pancreas, and propranolol treatment reversed glucose intolerance in these mice. Finally, re-expression of PREP by bilateral VMH injection of adeno-associated virus-PREP reversed the glucoseintolerant phenotype of the Prep~(gt/gt) mice. Taken together, our results unmask a previously unknown player in central regulation of glucose metabolism and pancreatic function.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第32期|11876-11881|共6页
作者
Jung Dae Kim; Chitoku Toda; Giuseppe DAgostinoCaroline J. ZeissRalph J. DiLeoneJohn D. ElsworthRichard G. KibbeyOwen ChanBrandon K. HarveyChristopher T. RichieMari SavolainenTimo My?h?nenJin Kwon JeongSabrina Diano;
展开▼
作者单位

Departments of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520;

Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520;

Departments of Psychiatry, Yale University School of Medicine, New Haven, CT 06520Departments of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224Faculty of Pharmacy, University of Helsinki, 00014, Helsinki, Finland;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
central glucose sensing; sympathetic nervous system; peripheral hormonal regulation;

Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice

摘要

著录项

相关主题

期刊订阅