MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review

Abstract

Background: Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. Objective: To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. Design: A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. Conclusions: From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50 000 pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults.

International Society of Sports Nutrition Position Stand: protein and exercise

“…The effect of insulin on MPS is dependent on its ability to increase amino acid availability, which does not occur when insulin is systematically increased (e.g., following feeding) [101]. In particular, insulin’s impact on net protein balance seems to operate most powerfully in an anti-catabolic manner on muscle [102].…”

Protein supplementation does not alter intramuscular anabolic signaling or endocrine response after resistance exercise in trained men

“…The lower dose of protein and carbohydrates in SUPP did not augment the cortisol, insulin, or growth hormone response following resistance exercise. Nevertheless, recent evidence suggests that transient hormonal responses may not promote a more favorable intramuscular anabolic environment [15,44]. The mechanisms of exercise-mediated muscle hypertrophy have been suggested to be solely an intrinsic process, whichmay not be influenced by transient changes in circulating hormones [13][14][15][16].…”

“…However, recent evidence has indicated thatsystemic hormonal concentrationsmay not promote a more favorable intramuscular anabolic environment [15,44].…”

Exercise and the Regulation of Skeletal Muscle Hypertrophy

“…25 Moreover, there is now significant data in human models to show that physiological increases in insulin concentrations, corresponding to those seen with ingestion of a meal, play a permissive, and not a stimulatory role in the regulation of MPS. 28,29 In our view, the physiological increases in growth hormone and insulin-like growth factor in response to resistance exercise may be similarly permissive, if they have a role at all, in mediating changes in rates of MPS.…”