| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print June 25, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00111.2002
Submitted on March 11, 2002
Accepted on June 20, 2002
1 Pediatrics, Rhode Island Hospital and Brown University, Providence, RI, USA
* To whom correspondence should be addressed. E-mail: Philip_Gruppuso{at}brown.edu.
Insulin has long been assigned a key role in the regulation of growth and metabolism during fetal life. Our prior observations indicated that hepatic insulin signaling is attenuated in the late gestation fetal rat. Therefore, we studied the perinatal ontogeny of hepatic insulin signaling extending from phosphatidylinositol 3-kinase (PI3K) to the ribosome. Initial studies demonstrated markedly decreased insulin-mediated activation of ribosomal protein S6 kinase 1 (S6K1) in the fetus. We found a similar pattern in the regulation of Akt, a kinase upstream from S6K1. Insulin produced minimal activation of IRS-1-associated PI3K activity in fetal liver. A modest IRS-2-associated response was seen in the fetus. However, levels of both IRS-1 and IRS-2 were very low in fetal liver relative to adult liver. IRS-1 content, and insulin responsiveness of PI3K, Akt and S6K1 showed a transition to the adult phenotype during the first several postnatal weeks. Examination of downstream insulin signaling to the translational apparatus showed marked attenuation, relative to the adult, of fetal hepatic insulin-mediated phosphorylation of 4E-BP1, the regulatory protein for the eIF4E initiation factor, and ribosomal protein S6. mTOR, a key integrator of nutritional and metabolic regulation of translation, was present in low amounts, was hypophosphorylated, and was not insulin-sensitive in the fetus. Our results indicate that protein synthesis during late gestation liver development may be mTOR- and insulin-independent. Re-examination of the role of insulin in fetal liver physiology may be warranted.
This article has been cited by other articles:
|
|
 |
|
  J. A. Sanders, A. Lakhani, C. Phornphutkul, K.-Y. Wu, and P. A. Gruppuso The effect of rapamycin on DNA synthesis in multiple tissues from late gestation fetal and postnatal rats Am J Physiol Cell Physiol, August 1, 2008; 295(2): C406 - C413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Gruppuso, S.-W. Tsai, J. M. Boylan, and J. A. Sanders Hepatic translation control in the late-gestation fetal rat Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R558 - R567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Anand and P. A. Gruppuso Rapamycin Inhibits Liver Growth during Refeeding in Rats via Control of Ribosomal Protein Translation but Not Cap-Dependent Translation Initiation J. Nutr., January 1, 2006; 136(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Sanders and P. A. Gruppuso Coordinated regulation of c-Myc and Max in rat liver development Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G145 - G155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A Maloney and W. D Rees Gene-nutrient interactions during fetal development Reproduction, October 1, 2005; 130(4): 401 - 410. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
