Table 1 Evidence for the role of known adipokines in mediating skeletal muscle insulin sensitivity

Leptin

Increased [25, 26, 127].

Overexpression of leptin in a skinny mouse model increased insulin sensitivity [29].

Administration of leptin (12–15 days) reversed insulin resistance in obese wistar rats [128].

Leptin reversed high fat diet induced skeletal muscle insulin resistance in rats, indirectly via reducing intramuscular triglycerides not though direct modulation of insulin signalling [129].

Recombinant leptin reduces IRS-1 phosphorylation and glucose uptake in L6 myotubes [27].

Increased phosphorylation of AKT in commercially available primary human myotubes [30].

Recombinant leptin increased glucose uptake in C2C12 myotubes [28].

Acute (10mins-1 h) stimulation of L6 Myotubes directly increased glucose uptake via a PI3K-dependent pathway. Leptin pre-treatment (10 min) of L6 myotubes inhibits insulin stimulated glucose uptake [130].

24 h Pre-treatment of L6 myotubes had no effect on glucose uptake but did inhibit adiponectin stimulated glucose uptake [131].

Adiponectin

Decreased [31, 32].

Adiponectin knockout mice demonstrate an obese and insulin resistant phenotype [37, 39].

Promotes glucose uptake in both C2C12 and L6 Myotubes [35, 36].

Induces fat oxidation through activation of AMPK in myotubes from lean subjects. Mechanism impaired in myotubes from T2D patients [41].

Systemic administration and overexpression of adiponectin drives increased insulin sensitivity in insulin resistant mice [38, 40].

Recombinant adiponectin increased glucose uptake via AMPK mediated reorganisation of the actin cytoskeleton and GLUT4 translocation via an independent mechanism [130].

Resistin

Increased [45, 46].

Administration of resistin (6 days) to wild type mice induces a state of insulin resistance [132].

Recombinant resistin Impaired insulin signalling and glucose uptake in both C2C12 and L6 myotubes [48, 49].

Unknown

Targeted reduction of resistin in insulin resistant mice via antisense oligodeoxynucleotide restored hepatic but not skeletal muscle insulin sensitivity [133].

Visfatin

Increased [134,135,136].

Visfatin overexpression in rats increased whole body insulin sensitivity and adipose tissue and liver IRS-1 phosphorylation in response to insulin [56].

Stimulated glucose uptake and increased GLUT4 membrane translocation and mRNA and protein expression in C2C12 myotubes via AMPK p38 MAPK signalling [57].

Unknown

Increased glucose uptake in rat EDL muscle [137].