Insulin infusion stimulates whole-body protein synthesis and activates the upstream and downstream effectors of mechanistic target of rapamycin signaling in the gluteus medius muscle of mature horses.

This study explores the role of insulin in regulating protein metabolism in horses, revealing that insulin significantly stimulates whole-body and muscle protein synthesis. The research also demonstrates that insulin activates key factors in the mechanistic target of rapamycin signaling pathway, an important cell growth control pathway, in the skeletal muscle of horses.

Study Objective and Methodology

• The primary goal of the research was to investigate the effects of different levels of insulin infusion on plasma amino acid concentrations and the activation of factors in the mechanistic target of rapamycin signaling pathway in horse skeletal muscles.
• The process called isoglycemic, hyperinsulinemic clamp procedures, a method that maintains blood glucose levels while manipulating blood insulin levels, was employed on 8 mature thoroughbred mares, undergoing four different rates of insulin infusion. These were categorized as CON (0 mU · kg(-1) · min(-1)), LOWINS (1.2 mU · kg(-1) · min(-1)), MEDINS (3 mU · kg(-1) · min(-1)), and HIGHINS (6 mU · kg(-1) · min(-1)).
• Throughout the procedure, blood samples were collected to measure plasma amino acid concentrations, and a biopsy from the gluteus medius muscle was taken at the end of the 2-hour clamp to measure the activation level of various intracellular proteins involved in protein synthesis such as protein kinase B, eukaryotic initiation factor 4E-binding protein 1, and riboprotein S6.

Main Findings

• Insulin’s influence on plasma amino acid concentrations was demonstrated as most essential amino acids decreased after 120 minutes of insulin infusion with the greatest decreases observed in horses receiving MEDINS and HIGHINS treatments.
• If the effects of insulin were simply metabolic (using up plasma amino acids), one would not expect an increase in the signaling proteins related to protein synthesis. But the authors observed increased activation (phosphorylation) of protein kinase B, 4E-binding protein 1, and riboprotein S6 with all three rates of insulin infusion as compared to CON, suggesting that these changes are linked to increased protein synthesis.
• The phosphorylation of these proteins reached the maximum level with MEDINS and HIGHINS treatments, supporting the conclusion that insulin stimulates protein synthesis in the skeletal muscles of mature horses.

Conclusion

• The research successfully shows that insulin plays a vital role in stimulating both whole-body and muscle protein synthesis in mature horses, thereby contributing significantly to our understanding of insulin’s impact on equine muscle metabolism.