Cytokines diabetes with insulin resistance

Adiponectin is a cytokine produced by adipocytes and is termed an "adipokine. Adiponectin functions as an insulin sensitizer. Downregulation of adiponectin receptors and low levels of adiponectin have been associated with obesity-linked insulin resistance (29). Exercise and dietary changes have been shown to raise low levels of adiponectin in obese adolescents (30). Additionally, sarpogrelate hydrochloride, a 5-HT2A antagonist, elevates low adiponectin levels and normalizes other factors associated with vascular changes seen in type 2 diabetes (31). 

Factors leading to characteristic dyslipidaemia are complex and not fully understood. Insulin resistance is associated with the failure of normal suppression of hormone-sensitive lipase in adipose tissue and increased lipolysis leading to increased flux of non-esterified fatty acids (NEFAs) to the liver this is partly responsible for increased hepatic output of very low-density lipoprotein (VLDL) [6]. Central obesity is common in insulin resistance and type 2 diabetes and visceral fat is increasingly recognised as an important paracrine and endocrine organ [7]. Adiponectin, an important adipose-specific adipokine, is reduced in insulin resistance and type 2 diabetes [8]. This would favour increased lipolysis as the action of a further important cytokine, TNF-alpha in stimulating lipolysis is unopposed. 

Endocrine In addition to peripheral insulin resistance and an impaired incretin effect, type 2 diabetes is associated with increased plasma levels of tumour necrosis factor alpha (TNFa). In a cross-over study on 10 healthy male volunteers, systemic inflammation induced by TNFa was used to examine any resultant alteration in the incretin hormone response to intravenous glucose. TNFa levels that induced symptoms of systemic inflammation increased plasma levels of this cytokine as well as levels of cortisol and IL-6 and increased the homeostasis model assessment of insulin resistance. By contrast, secretion of incretin hormones and the incretin effect remained unchanged [69 ]. 

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