Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 OC21


1Clinical Sciences Research Institute, UHCW Trust, Walsgrave, Coventry, UK; 2Heart Research Institute, Cardiff University, Wales, UK; 3Diabetes Centre, George Eliot Hospital NHS Trust, Nuneaton, UK; 4Warwick Hospital, NHS Trust, Warwick, UK.

Objective: The adipocytokine visfatin, expressed in abdominal adipose tissue (AT) is thought to mimic insulin activity. However, whilst central adiposity is closely related to insulin resistance (IR) and T2DM, visfatins’ role in the development of these conditions remains unclear.

Method: We investigated circulating visfatin levels in non-diabetic (ND) and diabetic (T2DM) subjects and in T2DM patients pre- and post- rosiglitazone (RSG) treatment. We further investigated the in vitro intracellular visfatin signalling mechanism in cultured human Abd Sc adipocytes, through the effect of insulin (Ins) ± RSG on visfatin, NFκB and phosphospecific-JNK1/2 protein expression, in addition to the influence NFκB and JNK inhibition on visfatin protein expression. We examined AT depot specificity and adiposity on visfatin protein expression, and the influence of human recombinant (hr) TNF-α & hrIL-6 on visfatin regulation in AbdSc adipocytes.

Results: T2DM subjects exhibited higher serum visfatin, TNF-α and IL-6 levels compared with ND controls (*P<0.05, ***P<0.001, ***P<0.001, respectively). Circulating visfatin and Ins levels were reduced post-RSG treatment (versus pre-treatment (*P=0.04)). Depot specific visfatin protein expression was observed (Om>Abd Sc; ***P<0.001). RSG10 nM/100 nMIns reduced visfatin, NFκB, and P-JNK1/2 protein expression (versus insulin alone (*P<0.05, **P<0.01, *P<0.05, respectively)). JNK inhibition reduced visfatin protein expression (*P<0.05), whilst NFκB inhibition increased visfatin expression (*P<0.05). Additionally, combined JNK & NFκB inhibitors reduced visfatin protein expression (***P<0.001). Only hrIL-6 treatment increased visfatin protein expression (versus control adipocytes (*P<0.05)).

Conclusions: These data indicate visfatin to be regulated by Ins/RSG, potentially through NFκB and JNK, representing an important insight into the metabolic regulation of visfatin in human AT. Furthermore IL-6 may also impact of visfatin regulation. Taken together, these data suggest that whilst visfatin does not appear to be a mere bystander in the pathogenesis of obesity and T2DM, its patho-biological and functional significance may depend on the metabolic state in which it is found.

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