High insulin combined with essential amino acids stimulates skeletal muscle mitochondrial protein synthesis while decreasing insulin sensitivity in healthy humans
MM Robinson, M Soop, TS Sohn… - The Journal of …, 2014 - academic.oup.com
MM Robinson, M Soop, TS Sohn, DM Morse, JM Schimke, KA Klaus, KS Nair
The Journal of Clinical Endocrinology & Metabolism, 2014•academic.oup.comContext: Insulin and essential amino acids (EAAs) regulate skeletal muscle protein
synthesis, yet their independent effects on mitochondrial protein synthesis (MiPS) and
oxidative function remain to be clearly defined. Objective: The purpose of this study was to
determine the effects of high or low insulin with or without EAAs on MiPS. Design: Thirty
participants were randomized to 3 groups of 10 each with each participant studied twice.
Study groups comprised (1) low and high insulin,(2) low insulin with and without EAAs, and …
synthesis, yet their independent effects on mitochondrial protein synthesis (MiPS) and
oxidative function remain to be clearly defined. Objective: The purpose of this study was to
determine the effects of high or low insulin with or without EAAs on MiPS. Design: Thirty
participants were randomized to 3 groups of 10 each with each participant studied twice.
Study groups comprised (1) low and high insulin,(2) low insulin with and without EAAs, and …
Context
Insulin and essential amino acids (EAAs) regulate skeletal muscle protein synthesis, yet their independent effects on mitochondrial protein synthesis (MiPS) and oxidative function remain to be clearly defined.
Objective
The purpose of this study was to determine the effects of high or low insulin with or without EAAs on MiPS.
Design
Thirty participants were randomized to 3 groups of 10 each with each participant studied twice. Study groups comprised (1) low and high insulin, (2) low insulin with and without EAAs, and (3) high insulin with and without EAAs.
Setting
The study was conducted in an in-patient clinical research unit.
Participants
Eligible participants were 18 to 45 years old, had a body mass index of <25 kg/m2, and were free of diseases and medications that might impair mitochondrial function.
Intervention
Low (∼6 μU/mL) and high (∼40 μU/mL) insulin levels were maintained by iv insulin infusion during a somatostatin clamp while maintaining euglycemia (4.7–5.2 mM) and replacing GH and glucagon. The EAA infusion was 5.4% NephrAmine. l-[ring-13C6]Phenylalanine was infused, and muscle needle biopsies were performed.
Main Outcomes
Muscle MiPS, oxidative enzymes, and plasma amino acid metabolites were measured.
Results
MiPS and oxidative enzyme activities did not differ between low and high insulin (MiPS: 0.07 ± 0.009 vs 0.07 ± 0.006%/h, P = .86) or between EAAs and saline during low insulin (MiPS: 0.05 ± 0.01 vs 0.07 ± 0.01, P = .5). During high insulin, EAAs in comparison with saline increased MiPS (0.1 ± 0.01 vs 0.06 ± 0.01, P < .05) and cytochrome c oxidase activity (P < .05) but not citrate synthase (P = .27). EAA infusion decreased (P < .05) the glucose infusion rates needed to maintain euglycemia during low (∼40%) and high insulin (∼24%).
Conclusion
EAAs increased MiPS and oxidative enzyme activity only with high insulin concentrations.
Oxford University Press