TitleHigh insulin combined with essential amino acids stimulates skeletal muscle mitochondrial protein synthesis while decreasing insulin sensitivity in healthy humans.
Publication TypeJournal Article
Year of Publication2014
AuthorsRobinson, MM, Soop, M, Sohn, TSeo, Morse, DM, Schimke, JM, Klaus, KA, K Nair, S
JournalJ Clin Endocrinol Metab
Date Published12/2014
KeywordsAdolescent, Adult, Amino Acids, Essential, Blood Glucose, Female, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Male, Middle Aged, Mitochondria, Muscle, Muscle Proteins, Muscle, Skeletal, Phenylalanine, Somatostatin, Young Adult

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/m(2), 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-(13)C6]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.

Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID25222757
PubMed Central IDPMC4255106
Grant ListR01 DK041973 / DK / NIDDK NIH HHS / United States
UL1TR000135 / TR / NCATS NIH HHS / United States
P30 DK050456 / DK / NIDDK NIH HHS / United States
U24 DK100469 / DK / NIDDK NIH HHS / United States
UL1 TR000135 / TR / NCATS NIH HHS / United States
T32 DK007352 / DK / NIDDK NIH HHS / United States
5R01DK041973 / DK / NIDDK NIH HHS / United States
U24DK100469 / DK / NIDDK NIH HHS / United States
5T32DK007352 / DK / NIDDK NIH HHS / United States