Lewandowski, K. C., Basinska-Lewandowska, M., Bienkiewicz, M., Randeva, Harpal S. and Lewinski, A.. (2008) Retinol-binding protein 4 (RBP-4) levels do not change after oral glucose tolerance test and after dexamethasone, but correlate with some indices of insulin resistance in humans. Endokrynologia Polska/Polish Journal of Endocrinology , Vol.59 (No.4). pp. 305-311. ISSN 0423–104X

Abstract

Abstract INTRODUCTION: Secretory products from adipocytes may contribute to deterioration in glycaemic control and increased insulin resistance (IR). Retinol-binding protein 4 (RBP-4) may increase IR in mice, with elevated levels in insulin-resistant mice and humans with obesity and type 2 diabetes. However, the mechanisms regulating RBP-4 synthesis remain not fully understood. It is not clear whether short-term glucose-induced hyperglycaemia and hyperinsulinaemia as well as glucocorticosteroid-induced increase in IR might be reflected in alterations in serum RBP-4 levels in humans. In order to investigate this, we measured serum RBP-4, glucose and insulin concentrations during 75.0 gram oral glucose tolerance test (OGTT) - Study 1, as well as before and after oral administration of dexamethasone - Study 2. MATERIAL AND METHODS: Both studies included 35 subjects (8 males), age (mean +/- SD) 39.1 +/- 15.6 years, BMI 35.8 +/- 8.7 kg/m(2). Twenty-four of those subjects (5 males), age 38.7 +/- 15.1 years, BMI 34.4 +/- 8.3 kg/m(2), had 75 gram oral glucose tolerance test (OGTT) - Study 1. Blood samples were taken before (0 minutes), and at 60 and 120 minutes of OGTT. 17 subjects (3 males, 4 subjects with type 2 diabetes), age 43.1 +/- 18.1 years, BMI 36.7 +/- 9.0 kg/m(2) underwent screening for Cushing's disease/syndrome (Study 2). Dexamethasone was administered in a dose of 0.5 mg every 6 hours for 48 hours. Fasting serum concentrations of RBP-4, glucose and insulin were assessed before (D0) and after 48 hours of dexamethasone administration (D2). IR was assessed by HOMA in all non-diabetic subjects and in subjects participating in study 1 also by Insulin Resistance Index (IRI), which takes into account glucose and insulin levels during OGTT. RESULTS: Glucose administration resulted in significant increases in insulin and glucose (p < 0.0001). There was, however, no change in RBP-4 concentrations (124.1 +/- 32 mg/ml at 0 minutes, 123 +/- 35 mg/ml at 60 minutes and 126.5 +/- 37.5 mg/ml at 120 minutes of OGTT, p = ns). All subjects in Study 2 achieved suppression of cortisol below 50 nmo/l. Dexamethasone administration resulted in an increase in fasting insulin (from 11.6 +/- 6.8 to 17.1 +/- 7.2 muU/ml; p = 0.003), and an increase in HOMA (from 2.73 +/- 1.74 to 4.02 +/- 2.27; p = 0.015), although without a significant change in RBP-4 levels (119 +/- 26.8 vs. 117.5 +/- 24.8 mg/ml, p = ns). RBP-4 correlated with fasting insulin (r = 0.40, p = 0.025), fasting glucose (r = 0.41, p = 0.02) and HOMA (r = 0.43, p = 0.015), but not with IRI (r = 0.19, p = 0.31). There was, however, only a moderate correlation between HOMA and IRI (r = 0.49 [r(2) = 0.24]; p = 0.006, Spearman rank correlation), while the best correlation was obtained between the product of glucose and insulin levels at 60 min of OGTT and IRI in a non-linear model (r = 0.94 [r(2) = 0.88]; p<0.00001). In subjects who received dexamethasone, a positive correlation between RBP-4 and HOMA (p = 0.01) was lost after two days of dexamethasone administration (p = 0.61). CONCLUSIONS: RBP-4 levels do not change during oral glucose tolerance test or after a dexamethasone-induced increase in insulin resistance. This implies that it is highly unlikely that RBP-4 is involved in short-term regulation of glucose homeostasis in humans and that it responds to short-term changes in insulin resistance. A moderate correlation between RBP-4 and some insulin resistance indices (HOMA) does not exclude the fact that RBP-4 might be one of many factors that can influence insulin sensitivity in humans.

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