BRX-220与吡格列酮在高脂饮食诱导的胰岛素抵抗中的胰腺外作用比较。

Comparison of the extrapancreatic action of BRX-220 and pioglitazone in the high-fat diet-induced insulin resistance.

作者信息

Seböková Elena, Kürthy Maria, Mogyorosi T, Nagy Karoly, Demcáková Edita, Ukropec Jozef, Koranyi Laszlo, Klimes Iwar

机构信息

Diabetes and Nutrition Research Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, SK-83306 Bratislava, Slovak Republic.

出版信息

Ann N Y Acad Sci. 2002 Jun;967:424-30. doi: 10.1111/j.1749-6632.2002.tb04298.x.

DOI:10.1111/j.1749-6632.2002.tb04298.x

PMID:12079870

Abstract

UNLABELLED

A new Biorex molecule, BRX-220, has been shown to be effective in animal models of diabetic neuro- and retinopathy. Recent in vitro studies showed that it might also have an insulin-sensitizing action. Therefore, the effect of BRX-220 on insulin sensitivity was compared with the action of pioglitazone (PGZ) in high fat (HF) diet-induced insulin resistance (IR) of rats.

METHODS

Male Wistar rats were fed for 3 weeks a standard chow (PD) or the HF (70-cal%) diet. The HF-fed rats were also given daily BRX-220 (20 mg/kg BW) or PGZ (6 mg/kg BW) by gavage. In vivo insulin action was assessed by the euglycemic hyperinsulinemic clamp. Glucose, insulin, FFA, triglyceride (TG), and glycerol levels in blood were also measured, as well as tissue TG content.

RESULTS

Increased levels of fed TG in circulation after HF diet (PD: 2.0+/-0.2 vs. HF: 5.0+/-0.8 mmol/L) were partially corrected by BRX-220 (HF + BRX: 3.8+/-0.3) and normalized by PGZ (HF + PGZ: 2.6+/-0.3). Both molecules prevented the increase in fed serum FFA levels after HF diet (PD: 0.5+/-0.06; HF: 1.8+/-0.2 mmol/L), with a more pronounced effect of PGZ (HF + BRX: 1.2+/-0.1; HF + PGZ: 0.7+/-0.06). Tissue TG levels increased significantly in response to HF feeding in both liver (HF: 16+/-3.0; PD: 6.4+/-1.1 micromol/g) and skeletal muscle (HF: 7.7+/-1.2; PD: 2.4+/-0.4). This increase was completely normalized by both agents in the liver (HF + BRX: 8.8+/-0.8; HF + PGZ: 8.8+/-1.0), and only partially in the skeletal muscles. HF diet-induced in vivo IR (PD: 25.4+/-0.5; HF: 15.7+/-0.5 mg/kg/min) was significantly reduced by BRX-220 (HF + BRX: 18.7+/-0.3) and PGZ (HF + PGZ: 22.8+/-0.4) treatment.

CONCLUSIONS

(1) Subchronic administration of BRX-220 leads to an improvement of in vivo insulin action. (2) This insulin-sensitizing effect is, however, not as pronounced as that of PGZ. (3) It is accompanied by a decrease of circulating TG and FFA levels in the postprandial state and (4) by lower TG content in liver and skeletal muscle.

摘要

未标注

一种新型生物瑞克斯分子BRX - 220已被证明在糖尿病神经病变和视网膜病变的动物模型中有效。最近的体外研究表明，它可能还具有胰岛素增敏作用。因此，将BRX - 220对胰岛素敏感性的影响与吡格列酮（PGZ）在高脂（HF）饮食诱导的大鼠胰岛素抵抗（IR）中的作用进行了比较。

方法

雄性Wistar大鼠分别喂食标准饲料（PD）或HF（70%热量）饮食3周。给喂食HF的大鼠每日经口灌胃给予BRX - 220（20mg/kg体重）或PGZ（6mg/kg体重）。通过正常血糖高胰岛素钳夹技术评估体内胰岛素作用。还测量了血液中的葡萄糖、胰岛素、游离脂肪酸（FFA）、甘油三酯（TG）和甘油水平以及组织TG含量。

结果

HF饮食后循环中进食后TG水平升高（PD：2.0±0.2 vs. HF：5.0±0.8mmol/L），BRX - 220使其部分恢复正常（HF + BRX：3.8±0.3），PGZ使其恢复正常（HF + PGZ：2.6±0.3）。两种分子均能防止HF饮食后进食后血清FFA水平升高（PD：0.5±0.06；HF：1.8±0.2mmol/L），PGZ的作用更明显（HF + BRX：1.2±0.1；HF + PGZ：0.7±0.06）。HF喂养使肝脏（HF：16±3.0；PD：6.4±1.1μmol/g）和骨骼肌（HF：7.7±1.2；PD：2.4±0.4）中的组织TG水平显著升高。两种药物均使肝脏中的这种升高完全恢复正常（HF + BRX：8.8±0.8；HF + PGZ：8.8±1.0），而在骨骼肌中仅部分恢复正常。HF饮食诱导的体内IR（PD：25.4±0.5；HF：15.7±0.5mg/kg/min）通过BRX - 220（HF + BRX：18.7±0.3）和PGZ（HF + PGZ：22.8±0.4）治疗显著降低。