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

Abstract

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 metaanalysis 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.)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 8.55], p=0.71), but significantly reduced MPB .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.

Link between blood flow and muscle protein metabolism in elderly adults

“…Insulin is a vasodilatory factor and has the dual effect of enhancing muscle protein synthesis and inhibiting breakdown 73,74) . Insulin promotes net muscle protein anabolism primarily by inhibiting protein breakdown, rather than by stimulating protein synthesis 73,74) .…”

“…Insulin is a vasodilatory factor and has the dual effect of enhancing muscle protein synthesis and inhibiting breakdown 73,74) . Insulin promotes net muscle protein anabolism primarily by inhibiting protein breakdown, rather than by stimulating protein synthesis 73,74) . In addition, insulin appears to have a permissive role in protein synthesis in the presence of elevated amino acid levels, and plays a clear role in reducing protein breakdown independent of amino acid availability 74) .…”

“…Insulin promotes net muscle protein anabolism primarily by inhibiting protein breakdown, rather than by stimulating protein synthesis 73,74) . In addition, insulin appears to have a permissive role in protein synthesis in the presence of elevated amino acid levels, and plays a clear role in reducing protein breakdown independent of amino acid availability 74) . However, insulin does not promote a positive net balance in elderly people 70) , because due to impaired suppression of protein breakdown by insulin stimulation 75) .…”

Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast

“…A later study (29) scrutinizing this issue reported that although whole body protein breakdown measured with leucine was similar after a 22-h fast in obese and lean women when calculated per LBM, muscle forearm leucine release per 100 ml of forearm tissue was dramatically (Ͼ50%) decreased in obese subjects and that AT accounted for up to 10% of whole body protein breakdown in both lean and obese subjects. It has been estimated that skeletal muscle contains between 30 and 45% of total body protein and contributes between 20 and 35% of whole body protein turnover (1). With fasting, it has been reported that up to 2 wk of starvation did not increase the leucine rate of appearance/protein breakdown in obese subjects, whereas 60 h of fasting resulted in higher leucine rates of appearance and oxidation rates in lean subjects (37).…”

Dysregulated homeostatic pathways in sarcopenia among frail older adults

“…Testosterone is well known to increase muscle mass by increasing the rate of muscle protein synthesis partly via stimulating IGF‐1 expression (Mudali & Dobs, 2004). Insulin appears to play a crucial role in maintaining the rate of muscle protein synthesis and breakdown, both in health and disease (Abdulla, Smith, Atherton, & Idris, 2016). Although the exact mechanism is not fully understood, as a key anabolic hormone, insulin stimulates muscle growth via secreting IGF‐1 followed by activation of the PI3K and Akt (also known as protein kinase B) signaling pathways via mammalian target of rapamycin (mTOR) that controls protein synthesis and the forkhead box O (FOXO) that controls protein degradation.…”