| Associations between body composition, circulating interleukin-1 receptor antagonist, osteocalcin, and insulin metabolism in active acromegaly. | |
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MedLine Citation:
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PMID: 19880791 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Patients with active acromegaly display a range of abnormalities in glucose metabolism. To elucidate interactions between bone and energy homeostasis in relation to excess GH, we sought to determine whether these patients were characterized by alterations in circulating levels of adipokines and cytokines and potential interactions with osteocalcin (OCN) and insulin resistance. METHODS: Forty-seven patients with active acromegaly: 26 women and 21 men (49 +/- 11, mean +/- sd) were evaluated and compared with age-, sex-, and body mass index-matched controls by x-ray absorptiometry, biochemical analysis [GH, IGF-I, OCN, leptin, adiponectin, retinol binding protein 4, IL-6, IL-1beta, and IL-1 receptor antagonist (IL-1Ra)], and glucose metabolism (homeostasis model assessment). In vitro effects of GH/IGF-I on IL-1beta/IL-1Ra in THP-1 macrophages and human white adipocytes as well as effects of GH/IGF-I in combination with carboxylated and undercarboxylated OCN on glucose-stimulated insulin release in human pancreatic islets were also investigated. RESULTS: Patients with acromegaly were characterized by markedly decreased serum levels of IL-1Ra and increased IL-1beta and IL-1beta to IL-1Ra ratio, suggesting enhanced IL-1 activity. The decreased IL-1Ra was strongly associated with increased OCN levels in multivariate models and was significantly correlated with decreased total body fat mass. In macrophages, IGF-I/GH significantly decreased the release of IL-1Ra and increased IL-1beta, suggesting that the decreased circulating IL-1Ra levels in acromegaly could reflect both direct and indirect mechanisms. Finally, circulating OCN was the main determinant of insulin resistance and beta-cell function in acromegaly and in vitro, a blunted insulin response was observed in the presence of OCN and GH/IGF-I. CONCLUSION: These data confirm and establish novel and complex interactions between bone, energy metabolism, and adipose tissue and suggest an unfavorable effect of OCN and GH/IGF-I in combination on insulin metabolism in active acromegaly. |
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Authors:
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Thor Ueland; Stine L Fougner; Kristin Godang; Tove Lekva; Leon J Schurgers; Hanne Scholz; Bente Halvorsen; Thomas Schreiner; Pål Aukrust; Jens Bollerslev |
Publication Detail:
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Type: Journal Article Date: 2009-10-30 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 95 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-08 Completed Date: 2010-02-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 361-8 Citation Subset: AIM; IM |
Affiliation:
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Section of Endocrinology, Research Institute for Internal Medicine, University of Oslo, N-0027 Oslo, Norway. thor.ueland@medisin.uio.no |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acromegaly
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blood*,
metabolism*,
physiopathology Adipokines / blood Adult Aged Body Composition / physiology* Case-Control Studies Cells, Cultured Cytokines / blood Female Human Growth Hormone / pharmacology Humans Insulin / blood, metabolism* Insulin Resistance / physiology Insulin-Like Growth Factor I / pharmacology Insulin-Secreting Cells / physiology Interleukin 1 Receptor Antagonist Protein / blood* Male Middle Aged Osteocalcin / blood*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Adipokines; 0/Cytokines; 0/IL1RN protein, human; 0/Interleukin 1 Receptor Antagonist Protein; 104982-03-8/Osteocalcin; 11061-68-0/Insulin; 12629-01-5/Human Growth Hormone; 67763-96-6/Insulin-Like Growth Factor I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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