RBP4: A Culprit for Insulin Resistance in End Stage Renal Disease That Can Be Cleared by Hemodiafiltration

Abstract

Introduction Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). In our study, we evaluated the association between RBP4 and IR in hemodialysis subjects (HD). We also assessed how circulating RBP4 could be influenced by kidney transplant or different dialytic techniques. Methods RBP4 serum levels were evaluated in HD (n = 16) and matched healthy controls (C; n = 16). RBP4 and glucose transporter type 4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating RBP4 was evaluated after kidney transplant (n = 7) and in hemodialysis patients (n = 10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF). Results HOMA index (P < 0.05) and serum RBP4 (P < 0.005) were higher in HD compared to C. RBP4 levels positively correlated with fasting serum glucose (P < 0.05). RBP4 mRNA was lower in HD compared to C (P < 0.05) and positively correlated with kidney function (P < 0.05) and GLUT4 mRNA (P < 0.001). Transplant or HDF reduced circulating RBP4 (P < 0.01 and P < 0.05, resp.). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels.

The synergistic effect of fenretinide and metformin to achieve a decrease in insulin resistance and inflammatory mediators: an in vivo study

“…This finding indicates that biomarkers of insulin sensitivity might be independently associated with glucose intolerance (De Leon et al 2018). Furthermore, a positive correlation was found between GLUT4 mRNA and RBP4 (R = −0.788), thereby aligning with the results of Grosjean et al (2017). However, this finding does not indicate an association with insulin levels.…”

“…Previous studies revealed that RBP4 increases the risk of insulin resistance in lean mice while RBP4deficient mice do not experience insulin resistance induced by a high-fat diet (Noy 2016;Codoner-Franch et al 2016). In accordance with the finding of Moraes-Vieira et al (2016), suppression of type 2 diabetes in mice with RBP4 was found to degrade insulin signaling in muscles, adipocytes, and liver (Grosjean et al 2017). Codoner-Franch et al (2016 found a strong correlation between the increase in serum RBP4 and obesity; this includes the obesity-related pathologies, inflammation, fatty liver disease, and insulin resistance.…”

Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review

“…Insulin resistance is associated with peripheral resistance of glucose uptake at the skeletal muscle site and manifests as impaired insulin signaling through the phosphorylation of insulin receptor substrate-1, which inhibits tyrosine kinase activity at the insulin receptor [ 181 , 183 ]. Another pathway of insulin resistance and impaired glucose metabolism may be suggested by high circulating retinol binding protein 4 (RBP4) [ 185 ]. Animal studies have demonstrated that RBP4′s inverse relationship with glucose transporter type 4 (GLUT4), which is insulin-dependent, induces glucose uptake in the fat and muscle [ 186 , 187 ].…”

“…Animal studies have demonstrated that RBP4′s inverse relationship with glucose transporter type 4 (GLUT4), which is insulin-dependent, induces glucose uptake in the fat and muscle [ 186 , 187 ]. High RBP4 has a role in glucose metabolism by inducing gluconeogenesis and inhibiting glucose uptake in the muscle via feedback suppression of adipose tissue expression, followed by reduced GLUT4 expression, which affects glucose uptake [ 185 ].…”

Comparative analysis of therapeutic effects between medium cut-off and high flux dialyzers using metabolomics and proteomics: exploratory, prospective study in hemodialysis

“…RBP4, a 21-kilodalton protein produced by adipocytes, is also chiefly excreted by the kidney and plays a pivotal role in insulin resistance (IR) 37 . In turn, IR is significantly associated with cardiovascular risk, and can significantly predict cardiovascular disease and mortality in dialysis patients 38 .…”