Insulin-like growth factor (IGF-II) is a polypeptide hormone with structural homology to insulin whose physiological functions are not clearly understood. IGF-II is thought to play an important role in fetal and placental development. The most compelling evidence concerning the role of IGF-II comes from transgenic mice with targeted disruption of the IGF-II gene (knockout mice). The phenotype of the IGF-II knockout mouse is growth retardation of both fetus and placenta during the last two-thirds of gestation. Although they are born approximately 60 percent the size of their normal littermates, they are normally-proportioned and fertile. In addition, the glycogen content of the placenta and fetal liver is greatly reduced in the knockout mouse suggesting that IGF-II may play an important role in the fetal carbohydrate metabolism. The overall goal of this proposal is to define the role of IGF-II in fetal hepatic carbohydrate metabolism and to elucidate some of the mechanisms by which this hormone may be exerting its effects. The IGF-II knockout mouse will be used to: 1) Determine whether IGF-II plays an important role in perinatal glycogen metabolism, 2) Determine some of the intracellular signaling pathways by which IGF-II stimulates glycogen synthesis. These studies should clarify the relationship between IGF-II and fetal carbohydrate metabolism, and its impact on perinatal growth. Defining the role of IGF-II and its effects on fetal growth will further understanding of the mechanisms and possible treatment of macrosomia and fetal growth retardation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK002653-02
Application #
6176105
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
1999-05-20
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
2
Fiscal Year
2000
Total Cost
$87,480
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Silva, Delia; Venihaki, Maria; Guo, Wei-Hui et al. (2006) Igf2 deficiency results in delayed lung development at the end of gestation. Endocrinology 147:5584-91