Abstract

Obesity is a major risk factor associated with insulin resistance [1-4]. The Visceral fat in obesity secretes various pro-inflammatory and pro-atherogenic adipokines resulting in chronic systemic inflammation and insulin resistance [5,6]. Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits production of proinflammatory adipokines, cytokines as well as inflammatory NF-κB activity through the receptor (IGFBP-3R), which may improve many metabolic disorders including insulin resistance in obesity [7,8]. However, the IGFBP-3/IGFBP-3R system appears to be dysregulated in obesity due to neutrophil serine protease (NSP)-induced IGFBP-3 proteolysis in circulation, thereby resulting in loss of its antiinflammatory function [8]. The complete characterization of the underlying mechanism of the NSP/ IGFBP-3/IGFBP-3R cascade in obesity will be benefit for identifying diagnostic and prognostic value of the IGFBP-3/IGFBP-3R axis and therapeutic potential of IGFBP-3R agonists and NSP inhibitors for insulin resistance.

Keywords: IGFBP-3; IGFBP-3R; Insulin resistance; Neutrophil serine proteases inhibitors

Abbreviations: T2DM: Diabetes Mellitus; CVD: Cardiovascular Disease; IR: Insulin Resistance; IGF: Insulin-like Growth Factor; IGFBPs: IGF-Binding Proteins; NSP: Neutrophil Serine Proteases; IGFBP-3R: IGFBP-3 Receptor