Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin

Abstract

Background: Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. Objective: The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). Methods: DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects (mean body mass index (BMI) 31.2±4.5 kg/m 2 , age 55 ± 7 years). The eight single-nucleotide polymorphisms (SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2 ± 3.5 kg/m 2 , age 57.7 ± 7.4 years). Results: Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. Conclusions: Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.

Oilseeds ameliorate metabolic parameters in male mice, while contained lignans inhibit 3T3-L1 adipocyte differentiation in vitro

“…Among the induced genes, adiponectin was up-regulated threefold and fourfold. Adiponectin levels have been shown to be associated with insulin-like growth factor-binding protein-5 (IGFBP-5), which modulates the insulin growth factor (IGF) signaling pathway in human subjects [48]. IGFs are important determinants of metabolic functions; thus, the recent identification of modulators of IGF bioactivity is of high interest.…”

Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus : A North Indian study

“…[11] Several genes were studied but only a handful showed conÞ rmed association, such as resistin, alpha-endosulfine, calpain10, peroxisome proliferators-activated receptor-gamma 2 (PPARγ-2), abundant transcript 1 gene (apM1), TCF7L2, insulin-like growth factor-binding protein 5 (IGFBP5), to name a few. [9,[12][13][14][15][16][17][18][19] Earlier studies on genetic polymorphisms in T2DM candidate genes were carried out among south Indians, in addition to those in the VDR gene. [20][21][22] VDR is a member of the steroid/thyroid hormone receptor family.…”

2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine (PhIP) induces gene expression changes in JAK/STAT and MAPK pathways related to inflammation, diabetes and cancer

“…For example, cFOS positively binds and activates STAT3, which positively activates EGR1, cFOS, and PTGS2 (COX-2). PhIP exposure suppressed this pathway, while it induced the expression of IBP5, a biomarker of obesity [36, 37], suggesting that the effects of PhIP exposure are complex. However, STAT3 can physically bind to and positively activate serum amyloid A1 binding proteins A1 and A2 (SAA1, SAA2) and these proteins were up-regulated by PhIP exposure.…”