| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
APPETITE, OBESITY, DIGESTION, AND METABOLISM
1Pediatrics/Neonatology, University of Colorado Health Sciences Center, Denver, Colorado; and 2Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California
Submitted 17 June 2004 ; accepted in final form 4 November 2004
To test the effects of acute fetal hyperinsulinemia on the pattern and time course of insulin signaling in ovine fetal skeletal muscle, we measured selected signal transduction proteins in the mitogenic, protein synthetic, and metabolic pathways in the skeletal muscle of normally growing fetal sheep in utero. In experiment 1, 4-h hyperinsulinemic-euglycemic clamps were conducted in anesthetized twin fetuses to produce selective fetal hyperinsulinemia-euglycemia in one twin and euinsulinemia-euglycemia in the other. Serial skeletal muscle biopsies were taken from each fetus during the clamp and assayed by Western blot for selected insulin signal transduction proteins. Tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and the p85 subunit of phosphatidylinositol 3-kinase doubled at 30 min and gradually returned to control values by 240 min. Phosphorylation of extracellular signal-regulated kinase 1,2 was increased fivefold through 120 min of insulin infusion and decreased to control concentration by 240 min. Protein kinase B phosphorylation doubled at 30 min and remained elevated throughout the study. Phosphorylation of p70 S6K increased fourfold at 30, 60, and 120 min. In the second experiment, a separate group of nonanesthetized singleton fetuses was clamped to intermediate and high hyperinsulinemic-euglycemic conditions for 1 h. GLUT4 increased fourfold in the plasma membrane at 1 h, and hindlimb glucose uptake increased significantly at the higher insulin concentration. These data demonstrate that an acute increase in fetal plasma insulin concentration stimulates a unique pattern of insulin signal transduction proteins in intact skeletal muscle, thereby increasing pathways for mRNA translation, glucose transport, and cell growth.
insulin signaling; fetal growth; glucose transporter 4
This article has been cited by other articles:
|
|
 |
|
  L. D. Brown, P. J. Rozance, J. S. Barry, J. E. Friedman, and W. W. Hay Jr. Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus Am J Physiol Endocrinol Metab, January 1, 2009; 296(1): E56 - E63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Zhu, B. Han, J. Tong, C. Ma, J. M. Kimzey, K. R. Underwood, Y. Xiao, B. W. Hess, S. P. Ford, P. W. Nathanielsz, et al. AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheep J. Physiol., May 15, 2008; 586(10): 2651 - 2664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. W. Limesand, P. J. Rozance, D. Smith, and W. W. Hay Jr. Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1716 - E1725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Bradford and M. S. Allen Depression in Feed Intake by a Highly Fermentable Diet Is Related to Plasma Insulin Concentration and Insulin Response to Glucose Infusion J Dairy Sci, August 1, 2007; 90(8): 3838 - 3845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Hay Jr Recent observations on the regulation of fetal metabolism by glucose J. Physiol., April 1, 2006; 572(1): 17 - 24. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
