Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice

Autores
Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly; de Nicola, Alejandro Federico; de Kloet, Edo Ronald
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Previous studies have demonstrated that type 1 diabetes is characterized by hypercorticism and lack of periodicity in adrenal hormone secretion. In the present study, we tested the hypothesis that hypercorticism is initiated by an enhanced release of ACTH leading subsequently to adrenocortical growth and increased output of adrenocortical hormones. To test this hypothesis, we used the streptozotocin (STZ)-induced diabetes mouse model and measured hypothalamic-pituitary-adrenal axis activity at different time points. The results showed that the expected rise in blood glucose levels induced by STZ treatment preceded the surge in corticosterone secretion, which took place 1 d after diabetes onset. Surprisingly, circulating ACTH levels were not increased and even below control levels until 1 d after diabetes onset and remained low until d 11 during hypercorticism. In response to ACTH (but not vasopressin), cultures of adrenal gland cells from 11-d diabetic mice secreted higher amounts of corticosterone than control cells. Real-time quantitative PCR revealed increased expression of melanocortin 2 and melanocortin 5 receptors in the adrenal glands at 2 and 11 d of STZ-induced diabetes. AVP mRNA expression in the paraventricular nucleus of the hypothalamus was increased, whereas hippocampal MR mRNA was decreased in 11-d diabetic animals. GR and CRH mRNAs remained unchanged in hippocampus and paraventricular nucleus of diabetic mice at all time points studied. These results suggest that sensitization of the adrenal glands to ACTH rather than an increase in circulating ACTH level is the primary event leading to hypercorticism in the STZ-induced diabetes mouse model.
Fil: Revsin, Yanina. Leiden University; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: van Wijk, Diane. Leiden University; Países Bajos
Fil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Oitzl, Melly. Leiden University; Países Bajos
Fil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: de Kloet, Edo Ronald. Leiden University; Países Bajos
Materia
Diabetes
Glucocorticoid Receptor
Mineralocorticoid Receptor
Acth
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25919
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/25919
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes miceRevsin, Yaninavan Wijk, DianeSaravia, Flavia EugeniaOitzl, Mellyde Nicola, Alejandro Federicode Kloet, Edo RonaldDiabetesGlucocorticoid ReceptorMineralocorticoid ReceptorActhhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Previous studies have demonstrated that type 1 diabetes is characterized by hypercorticism and lack of periodicity in adrenal hormone secretion. In the present study, we tested the hypothesis that hypercorticism is initiated by an enhanced release of ACTH leading subsequently to adrenocortical growth and increased output of adrenocortical hormones. To test this hypothesis, we used the streptozotocin (STZ)-induced diabetes mouse model and measured hypothalamic-pituitary-adrenal axis activity at different time points. The results showed that the expected rise in blood glucose levels induced by STZ treatment preceded the surge in corticosterone secretion, which took place 1 d after diabetes onset. Surprisingly, circulating ACTH levels were not increased and even below control levels until 1 d after diabetes onset and remained low until d 11 during hypercorticism. In response to ACTH (but not vasopressin), cultures of adrenal gland cells from 11-d diabetic mice secreted higher amounts of corticosterone than control cells. Real-time quantitative PCR revealed increased expression of melanocortin 2 and melanocortin 5 receptors in the adrenal glands at 2 and 11 d of STZ-induced diabetes. AVP mRNA expression in the paraventricular nucleus of the hypothalamus was increased, whereas hippocampal MR mRNA was decreased in 11-d diabetic animals. GR and CRH mRNAs remained unchanged in hippocampus and paraventricular nucleus of diabetic mice at all time points studied. These results suggest that sensitization of the adrenal glands to ACTH rather than an increase in circulating ACTH level is the primary event leading to hypercorticism in the STZ-induced diabetes mouse model.Fil: Revsin, Yanina. Leiden University; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: van Wijk, Diane. Leiden University; Países BajosFil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Oitzl, Melly. Leiden University; Países BajosFil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Kloet, Edo Ronald. Leiden University; Países BajosOxford University Press2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25919Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly; de Nicola, Alejandro Federico; et al.; Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice; Oxford University Press; Endocrinology; 149; 7; -1-2008; 3531-35390013-72271945-7170CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2007-1340info:eu-repo/semantics/altIdentifier/doi/ 10.1210/en.2007-1340info:eu-repo/semantics/altIdentifier/pmid/18420743info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:31Zoai:ri.conicet.gov.ar:11336/25919instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:55:31.516CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
title Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
spellingShingle Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
Revsin, Yanina
Diabetes
Glucocorticoid Receptor
Mineralocorticoid Receptor
Acth
title_short Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
title_full Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
title_fullStr Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
title_full_unstemmed Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
title_sort Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
dc.creator.none.fl_str_mv Revsin, Yanina
van Wijk, Diane
Saravia, Flavia Eugenia
Oitzl, Melly
de Nicola, Alejandro Federico
de Kloet, Edo Ronald
author Revsin, Yanina
author_facet Revsin, Yanina
van Wijk, Diane
Saravia, Flavia Eugenia
Oitzl, Melly
de Nicola, Alejandro Federico
de Kloet, Edo Ronald
author_role author
author2 van Wijk, Diane
Saravia, Flavia Eugenia
Oitzl, Melly
de Nicola, Alejandro Federico
de Kloet, Edo Ronald
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Diabetes
Glucocorticoid Receptor
Mineralocorticoid Receptor
Acth
topic Diabetes
Glucocorticoid Receptor
Mineralocorticoid Receptor
Acth
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Previous studies have demonstrated that type 1 diabetes is characterized by hypercorticism and lack of periodicity in adrenal hormone secretion. In the present study, we tested the hypothesis that hypercorticism is initiated by an enhanced release of ACTH leading subsequently to adrenocortical growth and increased output of adrenocortical hormones. To test this hypothesis, we used the streptozotocin (STZ)-induced diabetes mouse model and measured hypothalamic-pituitary-adrenal axis activity at different time points. The results showed that the expected rise in blood glucose levels induced by STZ treatment preceded the surge in corticosterone secretion, which took place 1 d after diabetes onset. Surprisingly, circulating ACTH levels were not increased and even below control levels until 1 d after diabetes onset and remained low until d 11 during hypercorticism. In response to ACTH (but not vasopressin), cultures of adrenal gland cells from 11-d diabetic mice secreted higher amounts of corticosterone than control cells. Real-time quantitative PCR revealed increased expression of melanocortin 2 and melanocortin 5 receptors in the adrenal glands at 2 and 11 d of STZ-induced diabetes. AVP mRNA expression in the paraventricular nucleus of the hypothalamus was increased, whereas hippocampal MR mRNA was decreased in 11-d diabetic animals. GR and CRH mRNAs remained unchanged in hippocampus and paraventricular nucleus of diabetic mice at all time points studied. These results suggest that sensitization of the adrenal glands to ACTH rather than an increase in circulating ACTH level is the primary event leading to hypercorticism in the STZ-induced diabetes mouse model.
Fil: Revsin, Yanina. Leiden University; Países Bajos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: van Wijk, Diane. Leiden University; Países Bajos
Fil: Saravia, Flavia Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Oitzl, Melly. Leiden University; Países Bajos
Fil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: de Kloet, Edo Ronald. Leiden University; Países Bajos
description Previous studies have demonstrated that type 1 diabetes is characterized by hypercorticism and lack of periodicity in adrenal hormone secretion. In the present study, we tested the hypothesis that hypercorticism is initiated by an enhanced release of ACTH leading subsequently to adrenocortical growth and increased output of adrenocortical hormones. To test this hypothesis, we used the streptozotocin (STZ)-induced diabetes mouse model and measured hypothalamic-pituitary-adrenal axis activity at different time points. The results showed that the expected rise in blood glucose levels induced by STZ treatment preceded the surge in corticosterone secretion, which took place 1 d after diabetes onset. Surprisingly, circulating ACTH levels were not increased and even below control levels until 1 d after diabetes onset and remained low until d 11 during hypercorticism. In response to ACTH (but not vasopressin), cultures of adrenal gland cells from 11-d diabetic mice secreted higher amounts of corticosterone than control cells. Real-time quantitative PCR revealed increased expression of melanocortin 2 and melanocortin 5 receptors in the adrenal glands at 2 and 11 d of STZ-induced diabetes. AVP mRNA expression in the paraventricular nucleus of the hypothalamus was increased, whereas hippocampal MR mRNA was decreased in 11-d diabetic animals. GR and CRH mRNAs remained unchanged in hippocampus and paraventricular nucleus of diabetic mice at all time points studied. These results suggest that sensitization of the adrenal glands to ACTH rather than an increase in circulating ACTH level is the primary event leading to hypercorticism in the STZ-induced diabetes mouse model.
publishDate 2008
dc.date.none.fl_str_mv 2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25919
Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly; de Nicola, Alejandro Federico; et al.; Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice; Oxford University Press; Endocrinology; 149; 7; -1-2008; 3531-3539
0013-7227
1945-7170
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25919
identifier_str_mv Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly; de Nicola, Alejandro Federico; et al.; Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice; Oxford University Press; Endocrinology; 149; 7; -1-2008; 3531-3539
0013-7227
1945-7170
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2007-1340
info:eu-repo/semantics/altIdentifier/doi/ 10.1210/en.2007-1340
info:eu-repo/semantics/altIdentifier/pmid/18420743
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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