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dc.contributor.authorGahete, Manuel D.
dc.contributor.authorCórdoba-Chacón, José
dc.contributor.authorLin, Qing
dc.contributor.authorBrüning, Jens C.
dc.contributor.authorKahn, C. Ronald
dc.contributor.authorCastaño, Justo P.
dc.contributor.authorChristian, Helen
dc.contributor.authorLuque, Raúl M.
dc.contributor.authorKineman, Rhonda D.
dc.date.accessioned2013-10-25T16:39:42Z
dc.date.available2014-07-07T09:30:13Z
dc.date.issued2013-07
dc.identifier.bibliographicCitationGahete MD, Córdoba-Chacón J, Lin Q, Brüning JC, Kahn CR, Castaño JP, Christian H, Luque RM, Kineman RD. Insulin and IGF-I inhibit GH synthesis and release in vitro and in vivo by separate mechanisms. Endocrinology. 2013 Jul;154(7):2410-20. doi: 10.1210/en.2013-1261.en_US
dc.identifier.issn0013-7227
dc.identifier.urihttp://hdl.handle.net/10027/10322
dc.descriptionThis is a copy of an article published in the Endocrinology © 2013 Endocrine Societyen_US
dc.description.abstractIGF-I is considered a primary inhibitor of GH secretion. Insulin may also play an important role in regulating GH levels because insulin, like IGF-I, can suppress GH synthesis and release in primary pituitary cell cultures and insulin is negatively correlated with GH levels in vivo. However, understanding the relative contribution insulin and IGF-I exert on controlling GH secretion has been hampered by the fact that circulating insulin and IGF-I are regulated in parallel and insulin (INSR) and IGF-I (IGFIR) receptors are structurally/functionally related and ubiquitously expressed. To evaluate the separate roles of insulin and IGF-I in directly regulating GH secretion, we used the Cre/loxP system to knock down the INSR and IGFIR in primary mouse pituitary cell cultures and found insulin-mediated suppression of GH is independent of the IGFIR. In addition, pharmacological blockade of intracellular signals in both mouse and baboon cultures revealed insulin requires different pathways from IGF-I to exert a maximal inhibitory effect on GH expression/release. In vivo, somatotrope-specific knockout of INSR (SIRKO) or IGFIR (SIGFRKO) increased GH levels. However, comparison of the pattern of GH release, GH expression, somatotrope morphometry, and pituitary explant sensitivity to acute GHRH challenge in lean SIRKO and SIGFRKO mice strongly suggests the primary role of insulin in vivo is to suppress GH release, whereas IGF-I serves to regulate GH synthesis. Finally, SIRKO and/or SIGFRKO could not prevent high-fat, diet-induced suppression of pituitary GH expression, indicating other factors/tissues are involved in the decline of GH observed with weight gainen_US
dc.description.sponsorshipThis work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Merit Award BX001114 and National Institutes of Health Grant R01DK088133 (to R.D.K.), “Sara Borrell” Program Grant CD11/00276 (to M.D.G.); Ministerios de Educacion y Ciencia e Innovación Grants RYC-2007-00186, JC2008- 00220, and BFU2008-01136/BFI (to R.M.L.), Grant BFU2010- 19300 (to J.P.C.) and Junta de Andalucía Grant BIO-0139/CTS- 5051 (to J.P.C.). Centro de Investigación Biomédica en Red is an initiative of the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (Spain).en_US
dc.language.isoen_USen_US
dc.publisherEndocrine Societyen_US
dc.titleInsulin and IGF-I Inhibit GH Synthesis and Release in Vitro and in Vivo by Separate Mechanismsen_US
dc.typeArticleen_US


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