Elevated serum RBP4 is associated with insulin resistance in women with polycystic ovary syndrome

Abstract

Retinol binding protein 4 (RBP4) is a novel adipocyte-secreted protein that contributes to systemic insulin resistance. Experiments in mice suggest that elevated RBP4 causes insulin resistance. In the present study, we determined serum RBP4 concentration and evaluated its association with insulin resistance in women with polycystic ovarian syndrome (PCOS); 39 PCOS women and 45 healthy control subjects were enrolled in this study. Serum RBP4, fasting plasma glucose (FPG) and fasting serum insulin (FINS) were measured in all subjects. Furthermore, oral glucose tolerance test (OGTT), Botnia clamp (an intravenous glucose tolerance test followed by an euglycemic hyperinsulinemic clamp), and measurements of sex hormones were performed in 13 control subjects and all the PCOS women. The levels of serum RBP4 were elevated in PCOS women compared with the control (11.69 +/- 6.72 versus 7.75 +/- 5.96 microg/mL, p = 0.006). RBP4 levels were positively correlated with WHR (r = 0.216, p = 0.048), and intravenous glucose tolerance test beta cell index (IVGTT-beta index) which reflected beta cell function (r = 0.309, p = 0.028), but were inversely correlated with M value during Botnia clamp, which represented insulin sensitivity (r = -0.362, p = 0.008). No correlation was found between RBP4 and age, BMI, blood pressure, FPG, FINS, 2-h postprandial glucose, 2-h postprandial insulin, free testosterone, total testosterone, follicle-stimulating hormone (FSH), or luteinizing hormone (LH). In a linear stepwise regression analysis with a model including age, BMI, WHR, free testosterone, IVGTT-beta index, and M value as independent variables, only M value showed significant correlation with serum RBP4 levels (r2 = 0.105, f = 6.640, p = 0.012). In conclusion, serum RBP4 levels are significantly increased in PCOS women and associated with insulin resistance, which indicates that RBP4 may be a contributing factor linking adipose tissue with insulin resistance in PCOS.

RBP4: a controversial adipokine

“…A possible direct role of gonadotropins on the expression of RBP4 is also proposed, as circulating RBP4 levels are higher in postmenopausal compared with premenopausal women and in women older than 50 years when compared with those younger than 50 years (35,86,87). Circulating RBP4 levels are increased in women with polycystic ovary syndrome (PCOS) and are correlated to increased levels of FSH and LH (88). In women with PCOS, RBP4 serum levels are positively correlated to serum levels of androgens (testosterone, 17-OH progesterone, and DHEA sulfate) (89).…”

Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance

“…It was performed 6-8 day after oral glucose tolerance test as described previously [18][19][20]: after fasting overnight, subjects were admitted to the hospital, where iv cannulas were placed in both arms for insulin and glucose infusion and for blood sampling. A priming dose of insulin was given followed by an infusion (120mIU/ m 2 /min) of short-acting human insulin (Lilly, Humulin, USA) for 120 min.…”

Elevated Serum Retinol Binding Protein 4 Level in Non-Obese Women with Polycystic Ovary Syndrome

“…16,26 In cer ta in stu di es that reported an in cre a se in le vels of RBP4 in sub jects with PCOS a cor re la tion has be en shown bet we en RBP4 and in su lin resis tan ce . 16,19 On the con trary, so me ot her investigations did not find any cor re la ti on bet ween increased RBP4 le vel and in su lin re sis tan ce. 17,18 Alt ho ugh we co uld not show any cor re la ti on betwe en the in cre a sed RBP4 le vels and in su lin re sistan ce, we ob ser ved that pa ti ents ha ving RBP4 le vels abo ve me di an va lu es we re mo re in su lin resis tant com pa red to ones ha ving le vels un der the me di an va lu e. In trin sic va ri a bi lity in in su lin re sistan ce me a su red with the HO MA met hod de tec ted hig her variability in pa ti ents with PCOS comTurkiye Klinikleri J Med Sci 2011;31 (2) pareked to nor mal wo men.…”

“…14,15 In ves ti ga ti ons which found higher le vels of RBP4 in cir cu la ti on in PCOS pa ti ents when compared to con trols, also report conflicting results abo ut the re la ti ons hip of this in cre a se with in su lin re sis tan ce, body mass index (BMI), fat mass and an dro ge ne mi a. [16][17][18][19] Further mo re, the se stu di es we re mostly performed on over we ight and obe se pa ti ents with PCOS. In our study, sin ce we con si der that non-obe se and obe se pa ti ents with PCOS ha ve dif fe rent me ta bo lic profi les, we ai med to in ves ti ga te RPB4 in pa ti ents having PCOS wit ho ut obe sity.…”