Thiazolidinedione addition reduces the serum retinol-binding protein 4 in type 2 diabetic patients treated with metformin and sulfonylurea.

Graduate Institute of Medicine, Kaohsiung Medical University Hospital, Taiwan.
Translational Research (Impact Factor: 4.04). 07/2008; 151(6):309-14. DOI: 10.1016/j.trsl.2008.04.003
Source: PubMed

ABSTRACT Retinol-binding protein 4 (RBP4) has been found to induce insulin resistance and to be increased in type 2 diabetes. Thiazolidinediones (TZDs) can improve insulin sensitivity through the activation of peroxisome proliferators-activated receptor-gamma (PPAR-gamma) and have been suggested as an adjunct to metformin (MF) and sulfonylurea (SU) in type 2 diabetes in a consensus statement from the ADA and EASD. Therefore, we investigated whether TZD could affect serum RBP4 level in type 2 diabetes already treated with MF and/or SU. Eighty-one type 2 diabetic patients were divided into 2 groups: (1) TZD group (n = 55): Pioglitazone 30 mg/day was given as an add-on medication; (2) SU group (n = 26): Gliclazide MR 30-120 mg or glimepiride 2-8 mg/day was prescribed. The average period of study was 97.1 days. Serum RBP4 and adiponectin were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. The addition of pioglitazone (TZD group) markedly decreased homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.021) compared with the SU group (P = 0.688). The change of RBP4 in the TZD group (-3.87 +/- 11.27 microg/mL) significantly differed from that in the SU group (2.52 +/- 8.24 microg/mL, P < 0.012). The increase of adiponectin in the TZD group (11.49 +/- 7.85 microg/mL) was apparently higher than that in the SU group (1.54 +/- 5.62 microg/mL, P < 0.001). Despite the change of glycosylated hemoglobin (HbA1c) did not differ (-0.77 +/- 1.3 vs -0.50 +/- 1.7, P = 0.446), the addition of pioglitazone could significantly lower serum RBP4 and HOMA-IR values, whereas an increased dosage of sulfonylurea agents did not alter HOMA-IR, RBP4, or adiponectin in type 2 diabetic patients who had been treated with metformin and/or sulfonylurea.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance. Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects. © 2015 S. Karger AG, Basel.
    Cellular Physiology and Biochemistry 01/2015; 35(2):778-88. DOI:10.1159/000369737 · 3.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is associated with metabolic derangements such as insulin resistance, inflammation and hypercoagulobility which can all be understood as consequences of adipose tissue dysfunction. The potential role for adipose tissue derived cytokines and adipokines in the development of vascular disease and diabetes may produce a clinical need to influence adipose tissue function. Various pharmacological and non-pharmacological interventions affect plasma cytokine and adipokine levels. The effects of these interventions depend on weight loss per se, changes in fat distribution without weight loss and/or direct effects on adipose tissue inflammation.Weight loss, as a result of diet, pharmacology and surgery, positively influences plasma adipokines and systemic inflammation. Several classes of drugs influence systemic inflammation directly through their anti-inflammatory actions. PPAR-γ agonism positively influences adipose tissue inflammation in several classes of intervention such as the thiazolidinediones and perhaps salicylates, CB1-antagonists and angiotensin II receptor blockers. Furthermore, within drug classes there are differential effects of individual pharmacologic agents on adipose tissue function.It can be concluded that several commonly used pharmacological and non-pharmacological interventions have unintended influences on adipose tissue function. Improving adipose tissue function may contribute to reducing the risk of vascular diseases and the development of type 2 diabetes.
    Cardiovascular Diabetology 01/2011; 10(1):13. DOI:10.1186/1475-2840-10-13 · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aims to evaluate the efficacy and safety of adding pioglitazone to treatment with metformin (MF) and gliclazide in patients with type 2 diabetes mellitus (DM2) who had inadequate glycemic control. This study is a retrospective cohort study based on King Abdullah University Hospital records concerning type 2 diabetic adult patients for year 2008. Patients included were assessed according to changes in glycosylated hemoglobin (HbA1c), lipid profile, albuminuria and liver enzymes before and after the addition of pioglitazone. The patients included in the study had an initial mean HbA1c of 9.44%, which decreased to 7.56% after the addition of pioglitazone (P-value < 0.005).
    Endocrine Research 02/2012; 37(1):7-11. DOI:10.3109/07435800.2011.566238 · 1.41 Impact Factor