Increased plasma retinol binding protein 4 levels in patients with inflammatory cardiomyopathy.
OBJECTIVE
Chronic heart failure (CHF) is associated with a higher risk for diabetes mellitus. Retinol binding protein 4 (RBP 4) is an adipose tissue-derived protein with pro-diabetogenic effects. A complete understanding of the association of CHF and insulin resistance remains elusive. The purpose of this study was to examine the relationship between CHF and diabetes mellitus.


RESULTS
Plasma levels of RBP 4, insulin, and interleukins (IL) 2, 8, and 10, were assessed in patients with dilated cardiomyopathy (DCM, n = 53), dilated inflammatory cardiomyopathy (DCMi, n = 54), and controls (n = 20). In addition, a possible mechanism of RBP 4 regulation was examined in adipocytes in vitro. Plasma levels of RBP 4 and insulin were measured by a specific ELISA. Interleukin concentrations were obtained by multiplex ELISA. Cell culture with 3T3-L1 adipocytes was performed to measure RBP 4 mRNA expression after stimulation with IL-8. RBP 4 levels were significantly increased in patients with DCMi (52.95 +/- 20.42 microg/mL) compared with DCM (35.54 +/- 23.08 microg/mL) and the control group (27.3 +/- 18.51 microg/mL). RBP 4 was positively correlated with IL-8 (r=0.416, P < 0.05) in human plasma in patients with DCMi. Moreover, increased insulin resistance was observed in patients with DCMi compared with the control and DCM groups. In vitro, IL-8 induced a significant upregulation of RBP 4 mRNA expression in adipocytes.


CONCLUSIONS
Elevated RBP 4 plasma concentrations, induced by IL-8, might be one mechanism leading to a higher incidence of diabetes in patients with DCMi.
Bobbert
Peter
P
Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. peter.bobbert@charite.de
Weithäuser
Alice
A
Andres
Janin
J
Bobbert
Thomas
T
Kühl
Uwe
U
Schultheiss
Heinz Peter
HP
Rauch
Ursula
U
Skurk
Carsten
C
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D000818:Animals; D009202:Cardiomyopathies / Q000097:blood* / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000097:blood; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000494:pharmacology; D008297:Male; D051379:Mice; D008875:Middle Aged; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis* / Q000378:metabolism
D007328:Insulin; D007376:Interleukin-2; D016209:Interleukin-8; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D016753:Interleukin-10