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: 5.03). 07/2008; 151(6):309-14. DOI: 10.1016/j.trsl.2008.04.003
Source: PubMed


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.

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    • "However, this possibility should not be ruled out. We have suggested that PC exerts its effect on PPAR in steatotic livers under warm hepatic ischemia (Casillas-Ramírez et al., 2008) and PPAR agonists reduce RBP4 levels in various pathologies (Yang et al., 2005; Teranishi et al., 2007; Lin et al., 2008). Only a full appraisal of the underlying protective mechanisms of PC can lead to both new pharmacological strategies to effectively protect steatotic liver grafts and new applications of PC in clinical practice of steatotic liver transplantation. "
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    ABSTRACT: Numerous steatotic livers are discarded for transplantation because of their poor tolerance of ischemia-reperfusion (I/R). The injurious effects of retinol-binding protein 4 (RBP4) in various pathologies are well documented. RBP4 levels are reduced by peroxisome proliferator-activated receptor-γ (PPARγ) agonists. Strategies aimed at increasing PPARγ protect steatotic livers under warm ischemia. Ischemic preconditioning (PC) based on brief periods of I/R protects steatotic liver grafts against I/R injury, but the responsible mechanism is poorly understood. We examined the roles of RBP4 and PPARγ in I/R injury associated with steatotic liver transplantation and the benefits of PC in such situations. We report that RBP4 and PPARγ expression levels in nonsteatotic livers were similar to those found in the sham group. However, reduced RBP4 and increased PPARγ levels were observed in steatotic livers. Treatment with either RBP4 or a PPARγ antagonist was effective only in steatotic livers. PC, which increased RBP4 levels, and RBP4 treatment both reduced PPARγ levels and hepatic injury in steatotic livers. When PPARγ was activated, neither RBP4 treatment nor PC (despite RBP4 induction) protected steatotic livers. In conclusion, steatotic liver grafts are more predisposed to down-regulate RBP4 and overexpress PPARγ. RBP4 treatment and PC, through RBP4 induction, reduced PPARγ levels in steatotic liver grafts, thus protecting them from the PPARγ detrimental effects.
    Full-text · Article · Jul 2011 · Journal of Pharmacology and Experimental Therapeutics
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    • "Also, PPAR-γ agonists may have indirect effects on insulin resistance by altering adipocytokine production. Pioglitazone increases high molecular weight adiponectin and decreases TNF-α levels and RBP-4 levels in patients with type 2 diabetes[155-157].In addition, this effect of pioglitazone on plasma levels of adiponectin is highly predictable on baseline levels[158]. Rosiglitazone increases leptin levels as would be expected due to the expansion of the SAT compartment and has effects on adipocytokine production as shown by lowering PAI-1 levels, which is partly dependent on adiponectin, and increasing adiponectin plasma levels [159-161]. "
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    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.
    Full-text · Article · Jan 2011 · Cardiovascular Diabetology
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    ABSTRACT: Background: Obesity is commonly associated with insulin resistance (IR), and is a common cause of type 2 diabetes. Adiponectin is an adipose tissue protein that enhances insulin sensitivity and has anti-atherogenic properties. Objective: This study was done to determine the adiponectin level and its relations to key components of the metabolic syndrome in obese diabetic (OD), obese non-diabetic (OB) and control (non-obese, non-diabetic (NOND)) Qatari subjects. Research design and Methods: We examined 64 (OD), 61 (OB) and 72 (NOND) male and female subjects. After a 12 h overnight fasting, blood samples were withdrawn for determination of plasma glucose, insulin, adiponectin, HbA1C, uric acid, total cholesterol, triglycerides, HDL-C and LDL-C. Results: Plasma levels of adiponectin in OD (10.60 ± 3.64µg/mL) and OB (11.21 ± 3.41µg/mL) were significantly lower than NOND controls (14.73 ± 4.97µg/mL). Significant, inverse correlations were observed between adiponectin levels and BMI (r=-0.241, p
    Full-text · Article · Jan 2008 · International Journal of Diabetes and Metabolism
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