Skip to main content
ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Research » Publications at this Location » Publication #322430

Title: Orosomucoid binds insulin and IGF1 and reduces hormone stimulated protein synthesis and glucose metabolism in C2C12 myotubes

item Ramsay, Timothy
item Elsasser, Theodore
item CAPERNA, THOMAS - Retired ARS Employee
item Blomberg, Le Ann

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/28/2018
Publication Date: N/A
Citation: N/A

Interpretive Summary: Selection for increased litter size in swine has resulted in a greater incidence of neonates exhibiting slower growth which has resulted in an approximate loss of 300 million pounds of pork annually in the United States. Biomarkers were needed that could predict postnatal growth rates at birth. Scientists at the Agricultural Research Service, Beltsville, Maryland, have shown that piglets that are small at birth or that grow slowly have an increased serum level of the protein, orosomucoid (ORM1) and have determined that ORM1 can function to reduce growth rates in neonatal pigs by specifically inhibiting the growth promoting functions of hormones, insulin and insulin-like growth factor 1 (IGF1), on skeletal muscle and fat. The binding of ORM1 to insulin and IGF1 reduced their ability to stimulate protein or fat synthesis, both critical processes for growth in the newborn. This research alters the basic concepts for the regulation of growth in newborn pigs, defined why ORM1 is a negative biomarker for growth, and provides a serum biomarker for genetic selection of high performance swine for use by universities, swine producers, swine breeders and swine nutrition companies.

Technical Abstract: Previous research has indicated that orosomuciod (ORM1) may enhance insulin response in 3T3-L1 adipocytes. The present study was undertaken to determine if ORM1 can modify muscle metabolism by examining glucose oxidation and protein synthesis in the C2C12 muscle cell line. Cells were used for experiments four days post fusion as myotubes. Myotubes were exposed to ORM1 for 24 hours, with the last four hours used to monitor 14C-glucose oxidation or the last 3 hours to measure protein synthesis by incorporation of 3H-tyrosine. Treatment of C2C12 myotubes with mouse ORM1 (0, 0.1, 1.0 or 10 µg/mL) had no effect on glucose oxidation or protein synthesis (p > 0.05; n = 4 trials). However; 10 µg ORM1/mL reduced insulin (10 nM) stimulated 14C-glucose oxidation and 3H-tyrosine incorporation (P< 0.05, n = 3 to 4 trials). In contrast, addition of 10 µg ORM1/mL medium did not reduce incorporation induced by 1 µM insulin (P > 0.05, n = 4 trials). Treatment with IGF1 (20 ng /mL) increased 3H-tyrosine incorporation (P < 0.01, n = 3 trials); while addition of ORM1 (10 µg/mL) reduced IGF1 induced incorporation (P < 0.01, n = 3 trials). Evaluation of ORM1 interactions with insulin and IGF1 using surface plasmon resonance (BiaCore®) analysis demonstrated that ORM1 specifically binds insulin ('2 = 0.116) or IGF1 ('2 = 0.442). These data indicate that ORM1 can indirectly reduce skeletal muscle metabolism by reducing the response to physiological concentrations of insulin or IGF1, in part by binding to these peptides.