title: Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK.
authors.forename: Haitham
authors.initials: H
authors.lastname: Abdulla
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Atherton
authors.affiliation: Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK. Iskandar.Idris@nottingham.ac.uk.
authors.forename: Iskandar
authors.initials: I
authors.lastname: Idris
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007333:Insulin Resistance; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010649:Phenylalanine / Q000097:blood / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine
keywords: Amino acids; Insulin; Meta-analysis; Muscle protein breakdown; Muscle protein synthesis; Systematic review