title: The possible role of mRNA expression changes of GH/IGF-1/insulin axis components in subcutaneous adipose tissue in metabolic disturbances of patients with acromegaly.
abstract: We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly.
authors.affiliation: Third Department of Medicine, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic, Institute of Endocrinology, Prague, Czech Republic. mhalu@lf1.cuni.cz.
authors.forename: V
authors.initials: V
authors.lastname: Touskova
authors.forename: J
authors.initials: J
authors.lastname: Klouckova
authors.forename: V
authors.initials: V
authors.lastname: Durovcova
authors.forename: Z
authors.initials: Z
authors.lastname: Lacinova
authors.forename: P
authors.initials: P
authors.lastname: Kavalkova
authors.forename: P
authors.initials: P
authors.lastname: Trachta
authors.forename: M
authors.initials: M
authors.lastname: Kosak
authors.forename: M
authors.initials: M
authors.lastname: Mraz
authors.forename: D
authors.initials: D
authors.lastname: Haluzikova
authors.forename: V
authors.initials: V
authors.lastname: Hana
authors.forename: J
authors.initials: J
authors.lastname: Marek
authors.forename: M
authors.initials: M
authors.lastname: Krsek
authors.forename: M
authors.initials: M
authors.lastname: Haluzik
mesh_terms: D000172:Acromegaly / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000097:blood*; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: C583557:IGF1 protein, human; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D058543:Class Ia Phosphatidylinositol 3-Kinase