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Publication type: Journal Article
Document type: Full Paper

Year: 1994

Author(s): Wolf, E; Kramer, R; Blum, WF; Föll, J; Brem, G

Title: Consequences of postnatally elevated insulin-like growth factor-II in transgenic mice: endocrine changes and effects on body and organ growth.

Source: Endocrinology (135), 5 1877-1886.



Authors Vetmeduni Vienna:

Brem Gottfried


Abstract:
Insulin-like growth factor-II (IGF-II) is an important regulator of embryonic growth and differentiation, but its function in postnatal life is unclear. To address this point, we generated transgenic mice harboring fusion genes in which a human IGF-II complementary DNA is placed under the transcriptional control of the rat phosphoenolpyruvate carboxykinase promoter. Transgene-specific messenger RNA was detected in liver, kidney, and several parts of the gut. Serum IGF-II levels in transgenic mice were 2-3 times higher than those in controls and increased after starvation. Circulating IGF-I correlated negatively and IGF-binding protein-e (IGFBP-2) positively with IGF-II levels, suggesting that IGF-I is displaced from IGFBPs by IGF-II and that IGF-II is a major regulator of IGFBP-2. Serum levels of IGFBP-3 and IGFBP-4 tended to be higher in phosphoenolpyruvate carboxykinase-IGF-II transgenic mice than in controls, as evaluated by ligand blot analysis. Starvation reduced serum IGF-I, but increased IGFBP-2 in transgenic mice more markedly than in controls. Fasting insulin levels were significantly reduced in transgenic mice, whereas glucose levels were not influenced by elevated IGF-II. The body growth of 4- and 12-week-old mice was not significantly influenced by elevated IGF-II, but transgenic mice displayed increased kidney and testis weight at the age of 4 weeks, and increased adrenal weight at the age of 12 weeks. Our results demonstrate that elevated IGF-II in postnatal life has multiple endocrine consequences and subtle time-specific effects on organ growth.

Keywords Pubmed: Animals - : Blood Glucose - analysis : Carrier Proteins - blood : DNA, Complementary - analysis : Fasting - physiology : Gene Expression Regulation - physiology : Gene Expression Regulation, Enzymologic - physiology : Growth - physiology : Insulin - blood : Insulin-Like Growth Factor Binding Protein 2 - blood : Insulin-Like Growth Factor Binding Protein 4 - blood : Insulin-Like Growth Factor Binding Proteins - blood : Insulin-Like Growth Factor I - analysis : Insulin-Like Growth Factor II - analysis : Mice - analysis : Mice, Transgenic - growth & development : Molecular Sequence Data - growth & development : Phosphoenolpyruvate Carboxykinase (GTP) - blood : RNA, Messenger - analysis : Radioimmunoassay - analysis

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