Insulin-Like Growth Factor Binding Protein–Related Protein 1 (IGFBP-rP1/MAC25) Is Linked to Endothelial-Dependent Vasodilation in High-Ferritin Type 2 Diabetes

López‐Bermejo, Abel; Khosravi, Javad; Ricart, Wifredo; Castro, Antoni; Hwa, Vivian; Pratt, Katherine L.; Casamitjana, Roser; Rosenfeld, Ron G.; Fernández-Real, José Manuel

doi:10.2337/dc06-1905

Cited by 7 publications

(7 citation statements)

References 22 publications

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“…We also found significant associations with WC, WHtR, SBP, DBP in control subjects. BMI and DBP had been found to be significant in previous study 28 40 . These associations have been modified potential confounders such as age, gender or additional HOMA-IR.…”

Section: Discussionmentioning

confidence: 68%

Serum IGFBP7 levels associate with insulin resistance and the risk of metabolic syndrome in a Chinese population

Liu

Ling

et al. 2015

Sci Rep

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Metabolic syndrome (MetS), one of the major public health concerns, is regarded as the “common soil” of incidence of common chronic diseases and may increase the risk of type 2 diabetes. The predominant underlying mechanism of MetS is insulin resistance (IR). Additionally, previous studies have indicated that IGFBP7 has high affinity of binding with insulin and might induce IR. The objective of this study was to firstly evaluate the associations of serum IGFBP7 levels with IR and MetS with a relatively large sample and population based design. In a population based MetS case-control study, HOMA-IR was used to evaluate the insulin sensitivity and serum IGFBP7 levels were determined with chemiluminescence–linked immunoassay. As a result, the subjects of MetS and IR had higher serum levels of IGFBP7 than control healthy subjects. High serum IGFBP7 levels increased the risk of MetS and IR. Serum IGFBP7 levels were also found to be significantly correlated with metabolic-associated parameters of Waist-to-hip ratio (WHR), HDL and LDL. These findings suggest that serum IGFBP7 levels are associated with IR and MetS, providing new insight into the mechanism of IR and Mets. IGFBP7 may be a potential interventional target for IR and Mets.

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Section: Discussionmentioning

confidence: 68%

Serum IGFBP7 levels associate with insulin resistance and the risk of metabolic syndrome in a Chinese population

Liu

Ling

et al. 2015

Sci Rep

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“…Other nomenclature for IGFBP7 includes menigioma-associated cDNA [ 21 ], tumor-derived adhesion factor [ 22 ], prostacyclin-stimulating factor [ 23 ], angiomodulin [ 24 ], and insulin-like growth factor (IGF)-binding protein-related protein 1 [ 25 , 26 ]. Besides these several functions referred to in these studies [ 21 – 26 ], IGFBP7 is distinct from other IGFBPs in that it exhibits a high and specific affinity for insulin [ 13 , 27 ] but a low affinity for IGF [ 28 ]. Then, IGFBP7 blocks insulin binding to the insulin receptor by inhibiting the early steps in insulin action [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Then, IGFBP7 blocks insulin binding to the insulin receptor by inhibiting the early steps in insulin action [ 27 ]. The association between IGFBP7 and type 2 diabetes was reported in two cross-sectional studies that indicated the positive correlation of serum IGFBP7 levels with insulin resistance [ 25 ] and endothelium-dependent vasodilation [ 26 ]. The present study is the first to report an association between urinary IGFBP7 and diabetic microangiopathy, i.e., DN.…”

Section: Discussionmentioning

confidence: 99%

Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells

et al. 2016

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Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN), and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs). Urine samples from Japanese patients with type 2 diabetes (n = 46) were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT). In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037), eGFR (r = −0.376, p = 0.01), urinary β2-microglobulin (r = 0.385, p = 0.008), and urinary N-acetyl-beta-D-glucosaminidase (NAG) (r = 0.502, p = 0.000). A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

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“…[16] measured serum IGFBP-7 levels in 43 men with T2D and 113 nondiabetic subjects and found increased serum IGFBP-7 levels to be associated with insulin resistance. One year later, the same research group [17] detected serum IGFBP-7 levels in 24 male T2D patients with high-ferritin and suggested that vascular function was linked to serum IGFBP-7 levels in these patients. In 2008, Kutsukake et al .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes

Hilding

et al. 2013

Clin Epigenet

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Insulin-Like Growth Factor Binding Protein–Related Protein 1 (IGFBP-rP1/MAC25) Is Linked to Endothelial-Dependent Vasodilation in High-Ferritin Type 2 Diabetes

Cited by 7 publications

References 22 publications

Serum IGFBP7 levels associate with insulin resistance and the risk of metabolic syndrome in a Chinese population

Serum IGFBP7 levels associate with insulin resistance and the risk of metabolic syndrome in a Chinese population

Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells

Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes

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