INSULIN/INSULIN-LIKE GROWTH FACTOR-1 HYBRID RECEPTOR ABUNDANCE DECREASES WITH DEVELOPMENT IN SUCKLING PIGS

Authors: SURYAWAN, AGUS - BAYLOR COLLEGE OF MED; NGUYEN, HANH - BAYLOR COLLEGE OF MED; ORELLANA, RENAN - BAYLOR COLLEGE OF MED; BUSH, JILL - BAYLOR COLLEGE OF MED; Davis, Teresa

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/20/2003
Publication Date: 9/1/2003
Citation: Suryawan, A., Nguyen, H.V., Orellana, R.A., Bush, J.A., Davis, T.A. 2003. Insulin/insulin-like growth factor-I hybrid receptor abundance decreases with development in suckling pigs. Journal of Nutrition. 133(9):2783-2787.

Interpretive Summary: In an earlier study, we found that the insulin signaling pathway is very active in the skeletal muscle of the neonate, and this activity decreases with development in conjunction with the developmental decrease in the response of muscle protein synthesis to insulin. Other studies have shown that in a state of insulin resistance, there is a heightened expression of hybrid insulin receptors. Each hybrid consists of a combination of half insulin receptor and half IGF-I receptor. Therefore, we thought it might be possible that the neonatal muscle, which is so sensitive to insulin, would acquire more hybrid receptors during the course of development, when the growing creature becomes increasingly resistant to insulin. We tested this theory in a piglet model and found, instead, that there were more hybrids in the muscle of 7-day-old piglets than in the 26-day-old piglets that we tested. Our results indicate that the abundance and activation of these hybrids do not contribute to the developmental decline in the activation of the insulin signaling pathway. This is important to know in doing research in this area, because our findings dispel a logical hypothesis regarding the function of these hybrid receptors in muscle as development continues, especially with respect to insulin resistance. Hybrid receptors are known to be elevated in diabetics, who have trouble controlling their blood insulin levels, and also in obese individuals, who are at risk for diabetes. These days, there is an expanding epidemic of obesity among both adults and children in the United States, and type 2 diabetes is growing rapidly at the same time. So scientists are working hard to understand as much as they can about factors affecting blood insulin levels. Thus, our findings will be very helpful to researchers pursuing answers to the question of what happens in the muscle of individuals who develop such chronic and costly health problems as obesity and diabetes, which are increasingly appearing in tandem.

Technical Abstract: The activation of the insulin signaling pathway that leads to translation initiation is enhanced in skeletal muscle of neonates and decreases with development in parallel with the developmental decline in muscle protein synthesis. Because the elevated expression of insulin receptor (IR)/insulin-like growth factor-I receptor (IGF-IR) hybrids has been associated with insulin resistance in some studies, we hypothesized that IR/IGF-IR hybrid abundance and binding affinity increase with development. To test this hypothesis, we determined the abundances and binding affinities of the IR, IGF-IR and hybrid receptor in skeletal muscle of 7- and 26-d-old pigs. We found that the abundances of IR, IGF-IR and hybrid receptor were higher in muscle of 7- than 26-d-old pigs. However, the relative proportions of hybrid receptor abundance compared with IR abundance and IGF-IR abundance was similar in both ages. The binding affinities of the IR, IGF-IR and hybrid receptor also were similar in both ages. Overall, the results suggest that insulin/IGF-I hybrid receptor abundance and binding affinity do not contribute to the developmental decline in the activation of the insulin signaling pathway.