Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice

Autores
Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly S.; de Nicola, Alejandro Federico; de Kloet, Ronald E.
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 S.. 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, Ronald E.. Leiden University; Países Bajos
Materia
Hypercorticism
Type 1 Diabetes
Brain
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:11336/25876
Acceder
id CONICETDig_2ce9846ec2377cbebec86d01055fa88b
oai_identifier_str oai:ri.conicet.gov.ar:11336/25876
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic miceRevsin, Yaninavan Wijk, DianeSaravia, Flavia EugeniaOitzl, Melly S.de Nicola, Alejandro Federicode Kloet, Ronald E.HypercorticismType 1 DiabetesBrainhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://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 S.. 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, Ronald E.. Leiden University; Países BajosOxford University Press2008-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25876Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly S.; de Nicola, Alejandro Federico; et al.; Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice; Oxford University Press; Endocrinology; 149; 7; 7-2008; 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 Técnicas2025-09-03T09:45:43Zoai:ri.conicet.gov.ar:11336/25876instacron: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 09:45:43.633CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
title Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
spellingShingle Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
Revsin, Yanina
Hypercorticism
Type 1 Diabetes
Brain
title_short Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
title_full Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
title_fullStr Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
title_full_unstemmed Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
title_sort Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice
dc.creator.none.fl_str_mv Revsin, Yanina
van Wijk, Diane
Saravia, Flavia Eugenia
Oitzl, Melly S.
de Nicola, Alejandro Federico
de Kloet, Ronald E.
author Revsin, Yanina
author_facet Revsin, Yanina
van Wijk, Diane
Saravia, Flavia Eugenia
Oitzl, Melly S.
de Nicola, Alejandro Federico
de Kloet, Ronald E.
author_role author
author2 van Wijk, Diane
Saravia, Flavia Eugenia
Oitzl, Melly S.
de Nicola, Alejandro Federico
de Kloet, Ronald E.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Hypercorticism
Type 1 Diabetes
Brain
topic Hypercorticism
Type 1 Diabetes
Brain
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
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 S.. 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, Ronald E.. 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 2008-07
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/11336/25876
Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly S.; de Nicola, Alejandro Federico; et al.; Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice; Oxford University Press; Endocrinology; 149; 7; 7-2008; 3531-3539
0013-7227
1945-7170
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25876
identifier_str_mv Revsin, Yanina; van Wijk, Diane; Saravia, Flavia Eugenia; Oitzl, Melly S.; de Nicola, Alejandro Federico; et al.; Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice; Oxford University Press; Endocrinology; 149; 7; 7-2008; 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
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
_version_ 1842268748368576512
score 13.13397

Publicaciones similares