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Medizin - Open Access LMU - Teil 11/22 Podcast
Consequences of Postnatally Elevated Insulin-Like Growth Factor-II in Transgenic Mice: Endocrine Changes and Effects on Body and Organ Growth.

Consequences of Postnatally Elevated Insulin-Like Growth Factor-II in Transgenic Mice: Endocrine Changes and Effects on Body and Organ Growth.

Medizin - Open Access LMU - Teil 11/22 vor 32 Jahren

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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-2
(IGFBP-2) positively with IGF-II levels, suggesting that IGF-I is
displaced from IGFBPs by IGF-II and that IGFII 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.