IGFBP-2 is an unglycosylated polypetide of 31.3 kDa and is one of the six circulating proteins that bind insulin-like growth factor (IGF)-I and -II with high affinity. Cleavage of signal peptide from the precursor protein generates the 31 kDa mature IGFBP-2, which consists of N- and C-terminal cysteine rich regions (1,2). Both N- and C-terminal regions of IGFBP-2 bind IGF-I and IGF-II preventing their interaction with IGF-1 receptor (2). IGFBP-2 mainly exists in non-glycosylated and non-phosphorylated form (3,4).
IGFBP-2 is a widely expressed protein with functions in bone and skeletal muscle development, and regulation of body growth and composition (5). Pure congenic IGFBP2 -/- mice show gender and bone compartment-specific phenotypes (6). IGFBP-2 overexpression mice have reduced body weight suggesting a role in postnatal growth by potentially regulating IGF-I bioavailability (7).
IGFBP-2 levels in circulation are influenced under different metabolism and malignant states (5). IGFBP-2 levels are high in cord serum from term infants, in contrast plasma IGFBP-2 levels in adults are lower (8). IGFBP-2 levels in adults are subjected to minimal daily fluctuations suggesting that postprandial changes in glucose and insulin levels do not influence IGFBP-2 levels (8). Compared to normal adults, IGFBP-2 levels are elevated in hypopituitary adults suggesting regulation by growth hormone (8). Extreme physical exercise results in elevated serum IGFBP-2 levels in men and women (5). Circulating IGFBP-2 levels are high in anorexia nervosa patients and suppressed in obesity and Type 2 diabetes (5). Overexpression of IGFBP-2 protects against obesity and diabetes by inhibiting adipogenesis and modulating insulin sensitivity (9,10). In contrast to Type 2 diabetes, IGFBP-2 levels are increased in Type 1 diabetes suggesting regulation by insulin sensitivity (11). Low postpartum IGFBP-2 levels are associated with the development of Type 2 diabetes in women with history of gestational diabetes mellitus (12).
IGFBP-2 levels are also altered in intra-uterine growth retardation (IUGR) and small for gestational age (SGA) cases. In IUGR cord serum levels of IGFBP-2 are elevated and levels are low in pre-pubertal and pubertal SGA subjects (5). IGFBP-2 role in cancer progression is indicated by elevated levels in several malignancies like prostate, ovarian, breast and gastric cancer (5). In colon cancer IGFBP-2 levels are elevated in plasma and is associated with increased risk of mortality (13). Recently, IGFBP-2 was identified as an early stage biomarker in invasive ductal adenocarcinoma of pancreas (14) and elevated serum IGFBP-2 levels were reported in idiopathic pulmonary fibrosis and Lupus nephritis patients (15,16). Circulating levels of IGFBP-2 may be an important biomarker of different metabolic and malignant states.
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