Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

Diabetologia. 2016 Jan;59(1):44-55. doi: 10.1007/s00125-015-3751-0. Epub 2015 Sep 24.


Aims/hypothesis: We aimed to investigate the role of insulin in regulating human skeletal muscle metabolism in health and diabetes.

Methods: We conducted a systematic review and meta-analysis of published data that examined changes in skeletal muscle protein synthesis (MPS) and/or muscle protein breakdown (MPB) in response to insulin infusion. Random-effects models were used to calculate weighted mean differences (WMDs), 95% CIs and corresponding p values. Both MPS and MPB are reported in units of nmol (100 ml leg vol.)(-1) min(-1).

Results: A total of 104 articles were examined in detail. Of these, 44 and 25 studies (including a total of 173 individuals) were included in the systematic review and meta-analysis, respectively. In the overall estimate, insulin did not affect MPS (WMD 3.90 [95% CI -0.74, 8.55], p = 0.71), but significantly reduced MPB (WMD -15.46 [95% CI -19.74, -11.18], p < 0.001). Overall, insulin significantly increased net balance protein acquisition (WMD 20.09 [95% CI 15.93, 24.26], p < 0.001). Subgroup analysis of the effect of insulin on MPS according to amino acid (AA) delivery was performed using meta-regression analysis. The estimate size (WMD) was significantly different between subgroups based on AA availability (p = 0.001). An increase in MPS was observed when AA availability increased (WMD 13.44 [95% CI 4.07, 22.81], p < 0.01), but not when AA availability was reduced or unchanged. In individuals with diabetes and in the presence of maintained delivery of AA, there was a significant reduction in MPS in response to insulin (WMD -6.67 [95% CI -12.29, -0.66], p < 0.05).

Conclusions/interpretation: This study demonstrates the complex role of insulin in regulating skeletal muscle metabolism. Insulin appears to have a permissive role in MPS in the presence of elevated AAs, and plays a clear role in reducing MPB independent of AA availability.

Keywords: Amino acids; Insulin; Meta-analysis; Muscle protein breakdown; Muscle protein synthesis; Systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Humans
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Resistance
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Phenylalanine / blood
  • Phenylalanine / chemistry
  • Signal Transduction


  • Insulin
  • Muscle Proteins
  • Phenylalanine