Skip navigation
Skip navigation

Modulation of pancreatic islets-stress axis by hypothalamic releasing hormones and 11 beta-hydroxysteroid dehydrogenase

Schmid, Janine; Ludwig, Barbara; Schally, Andrew V.; Steffen, Anja; Ziegler , Christian G; Block, Norman L; Koutmani, Yassemi; Brendel, Mathias D; Karalis, Katia P; Simeonovic, Charmaine; Licinio, Julio; Ehrhart-Bornstein, Monika; Bornstein, SR

Description

Corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GHRH), primarily characterized as neuroregulators of the hypothalamic- pituitary-adrenal axis, directly influence tissue-specific receptor-Systems for CRH and GHRH in the endocrine pancreas. Here, we demonstrate the expression of mRNA for CRH and CRH-receptor type 1 (CRHR1) and of protein for CRHR1 in rat and human pancreatic islets and rat insulinoma cells. Activation of CRHR1 and GHRH-receptor significantly increased...[Show more]

dc.contributor.authorSchmid, Janine
dc.contributor.authorLudwig, Barbara
dc.contributor.authorSchally, Andrew V.
dc.contributor.authorSteffen, Anja
dc.contributor.authorZiegler , Christian G
dc.contributor.authorBlock, Norman L
dc.contributor.authorKoutmani, Yassemi
dc.contributor.authorBrendel, Mathias D
dc.contributor.authorKaralis, Katia P
dc.contributor.authorSimeonovic, Charmaine
dc.contributor.authorLicinio, Julio
dc.contributor.authorEhrhart-Bornstein, Monika
dc.contributor.authorBornstein, SR
dc.date.accessioned2015-12-07T22:15:03Z
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/1885/17729
dc.description.abstractCorticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GHRH), primarily characterized as neuroregulators of the hypothalamic- pituitary-adrenal axis, directly influence tissue-specific receptor-Systems for CRH and GHRH in the endocrine pancreas. Here, we demonstrate the expression of mRNA for CRH and CRH-receptor type 1 (CRHR1) and of protein for CRHR1 in rat and human pancreatic islets and rat insulinoma cells. Activation of CRHR1 and GHRH-receptor significantly increased cell proliferation and reduced cell apoptosis. CRH stimulated both cellular content and release of insulin in rat islet and insulinoma cells. At the ultrastructural level, CRHR1 stimulation revealed a more active metabolic state with enlarged mitochondria. Moreover, glucocorticoids that promote glucose production are balanced by both 11b-hydroxysteroid dehydrogenase (11β-HSD) isoforms; 11β-HSD-type-1 and 11β-HSD-type-2. We demonstrated expression of mRNA for 11β-HSD-1 and 11β-HSD-2 and protein for 11β-HSD-1 in rat and human pancreatic islets and insulinoma cells. Quantitative real-time PCR revealed that stimulation of CRHR1 and GHRH-receptor affects the metabolism of insulinoma cells by downregulating 11β-HSD-1 and up-regulating 11β-HSD-2. The 11β-HSD enzyme activity was analyzed by measuring the production of cortisol from cortisone. Similarly, activation of CRHR1 resulted in reduced cortisol levels, indicating either decreased 11β-HSD-1 enzyme activity or increased 11β-HSD-2 enzyme activity; thus, activation of CRHR1 alters the glucocorticoid balance toward the inactive form. These data indicate that functional receptor systems for hypothalamic-releasing hormone agonists exist within the endocrine pancreas and influence synthesis of insulin and the pancreatic glucocorticoid shuttle. Agonists of CRHR1 and GHRH-receptor, therefore, may play an important role as novel therapeutic tools in the treatment of diabetes mellitus.
dc.publisherNational Academy of Sciences (USA)
dc.rightsAuthor/s retain copyright
dc.sourcePNAS - Proceedings of the National Academy of Sciences of the United States of America
dc.subjectKeywords: 11beta hydroxysteroid dehydrogenase; 11beta hydroxysteroid dehydrogenase 1; 11beta hydroxysteroid dehydrogenase 2; corticotropin releasing factor; corticotropin releasing factor receptor 1; glucocorticoid; glucose; insulin; messenger RNA; animal cell; ani Islet proliferation; Metabolic syndrome; Regenerative therapy
dc.titleModulation of pancreatic islets-stress axis by hypothalamic releasing hormones and 11 beta-hydroxysteroid dehydrogenase
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume108
dc.date.issued2011
local.identifier.absfor110306 - Endocrinology
local.identifier.ariespublicationu4492120xPUB2
local.type.statusPublished Version
local.contributor.affiliationSchmid, Janine, Univ Hosp Carl Gustav Carus
local.contributor.affiliationLudwig, Barbara, University Hospital Carl Gustav Carus
local.contributor.affiliationSchally, Andrew V., Univ Miami, Miller Sch Med
local.contributor.affiliationSteffen, Anja, University Hospital Carl Gustav Carus
local.contributor.affiliationZiegler , Christian G, University Hospital Carl Gustav Carus
local.contributor.affiliationBlock, Norman L, University of Miami
local.contributor.affiliationKoutmani, Yassemi, Academy Athens
local.contributor.affiliationBrendel, Mathias D, Univ Hosp Carl Gustav Carus
local.contributor.affiliationKaralis, Katia P, Harvard Univ, Sch Med
local.contributor.affiliationSimeonovic, Charmaine, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLicinio, Julio, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationEhrhart-Bornstein, Monika, University of Dresden
local.contributor.affiliationBornstein, SR, University of Dresden
local.bibliographicCitation.issue33
local.bibliographicCitation.startpage13722
local.bibliographicCitation.lastpage13727
local.identifier.doi10.1073/pnas.1110965108
local.identifier.absseo970117 - Expanding Knowledge in Psychology and Cognitive Sciences
dc.date.updated2016-02-24T11:10:43Z
local.identifier.scopusID2-s2.0-80052009174
local.identifier.thomsonID000293895100072
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Schmid_Modulation_of_pancreatic_2011.pdf1.34 MBAdobe PDF


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator