We have continued our study of the insulin-like growth factor, rat IGF-II. During the past year, we have demonstrated that: (1) multiple IGF-II RNAs (1.2 to 5 kb) arise from a single gene through the use of 2 promoters and alternate polyA addition sites; (2) the IGF-II gene is transcribed from both promoters in 11 fetal rat tissues with different efficiencies. Transcription from both promoters is high in the fetus and early neonate and negligible in adult tissues; (3) 1.2 kb IGF-II RNA is translated into Mr 22,000 pre-pro-rIGF-II, whereas 4 and 5 kb IGF-II RNAs are not translationally competent; (4) IGF-II RNA is translated in different tissues, and pre-pro-rIGF-II processed to Mr 7484 biologically active IGF-II; (5) the fetal/neonatal form of the IGF carrier protein is synthesized as a Mr 35,000 precursor in cell-free translation, and cotranslationally processed to the stable, secreted Mr 33,000 form; (6) translatable RNA encoding the Mr 35,000 carrier protein precursor is present in fetal and neonatal rat liver, but not in adult liver, suggesting that developmental regulation occurs at the level of transcription; (7) polyclonal antibodies to purified type II receptor do not stimulate or inhibit IGF actions in L6 rat myoblasts, suggesting that these effects are not mediated by the type II receptor; (8) nearly full-size type II IGF receptors circulate in fetal and neonatal rat serum, and that levels of circulating receptor decrease markedly in older rats; (9) IGF-II potently stimulates neurite outgrowth in sympathetic and sensory neurons cultured from chick embryos; (10) activation of human T lymphocytes results in increased expression of type I and type II IGF receptors, suggesting that the IGFs may participate in the activation cascade; (11) two-chain insulin-IGF hybrid molecules containing the B-domain of IGF-I have increased mitogenic activity and binding to type I IGF receptors but do not bind to IGF carrier proteins.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
1987
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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Adams, Ted D; Pendleton, Robert C; Strong, Michael B et al. (2010) Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese. Obesity (Silver Spring) 18:121-30
Hammoud, Ahmad; Carrell, Douglas T; Meikle, A Wayne et al. (2010) An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men. Fertil Steril 94:1734-8

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