Table 2.

Evidence for the role of novel adipokines in mediating insulin sensitivity

Adipokine	Association with obesity and/or T2D in humans	Adipokine effect on insulin signalling in animal models		Adipokine effect on insulin signalling in human skeletal muscle
		In Vivo	In Vitro
FGF-21	Increased [86].	Increased insulin sensitivity and glucose uptake in mice, via FGF-21 mediated increases in adiponectin production and secretion from adipocytes [76].	6 h incubation of mouse EDL muscle with FGF-21 resulted in a 54% increase in insulin stimulated glucose uptake [86].	Directly increased glucose uptake in primary human myotubes [86]. Prevents palmitate-induced insulin resistance in primary human myotubes by inhibiting stress kinases and NF-κB [87].
		Continuous cerebral administration for 2 weeks increased whole body insulin sensitivity in rats with dietary induced obesity [77].
		Daily administration for 6 weeks improved glucose handling in diabetic rhesus monkeys [78].
Chemerin	Increased [94, 138].	Overexpression increased insulin resistance in LDL receptor deficient mice by reducing AKT phosphorylation in response to insulin in skeletal muscle, but not liver or pancreas [96].	24 h pre-treatment reduces insulin stimulated glucose uptake in C2C12 myotubes in a dose dependent manor [99].	24 h chemerin Increased insulin resistance and reduced insulin stimulated glucose uptake in primary human myotubes, mediated by increased ERK signalling [95].
		knockout mice display increased skeletal muscle insulin resistance while transgenic mice exhibit increased skeletal muscle insulin resistance [98].
		Acute chemerin treatment exacerbated glucose intolerance and lowered serum insulin levels in obese and diabetic mice. No effect observed in normoglycemic mice [97].
CTRP3	Decreased [115, 116, 139].	Administration of recombinant CTRP3 directly lowers glucose levels in normal and insulin-resistant ob/ob mice [140].	Administration of recombinant CTRP3 to L6 myotubes had no effect on glucose uptake [140].	Unknown
		Overexpression of CTRP3 improved insulin sensitivity in HFD fed mice [141].	Increased glucose uptake and GLUT 4 mRNA expression in insulin resistant adipocytes [142].
RBP4	Increased [143, 144].	Overexpression or direct administration of RBP4 increased insulin resistance in mice. RBP4 knockout improves insulin sensitivity in mice [144].	unknown	Unknown
		Reducing circulating RBP4 in obese mice models improved glucose tolerance and increased insulin stimulated glucose uptake in skeletal muscle up to 60% [145].
Vaspin	Increased [65, 67, 68].	Vaspin treatment increased insulin sensitivity and glucose tolerance in obese and diabetic mice [59, 60].	Unknown	Unknown
		transgenic mice overexpressing vaspin displayed improved glucose tolerance and were protected from obesity when challenged with a high fat diet [62].
Pref-1	Increased [101].	Overexpression in mice drives insulin resistance via decreased adipose tissue and skeletal muscle glucose uptake and impaired skeletal muscle insulin signalling [105].	Unknown	4 Day exposure to primary human myotubes from lean, obese and T2D subjects had no effect on glucose uptake [106].
Follistatin-like 1	Increased [108].	Unknown	Blunts insulin signalling-adipocytes [108].	unknown
Omentin-1	Decreased [146, 147].	Unknown	omentin-1 induced AKT phosphorylation and enhanced insulin-stimulated glucose uptake in human adipocytes [123].	Unknown Unknown
Lipocallin-14	Unknown	Over expression in diet induced obese mice reduced glucose and insulin levels while improving glucose tolerance [124].	Unknown