葡萄糖转运蛋白4与骨骼肌、脂肪组织胰岛素抵抗的关系

胰岛素抵抗（Insulin resistance，IR）是2型糖尿病的一个重要的病理特征，其定义是正常或高分泌量的胰岛素产生低于正常生物效应的一种状态，表现为肝脏、肌肉、脂肪等外周组织对葡萄糖的代谢障碍，其中骨骼肌对葡萄糖利用依赖于胞膜上的运载蛋白，葡萄糖转运蛋白4（GLUT4）是主要的葡萄糖运载体，其所介导的葡萄糖转运是骨骼肌糖代谢的主要限速步骤，因此GLUT4对于全身血糖内稳态的调控具有重要意义。     

葫芦巴籽和桑叶提取混合物对胰岛素抵抗糖脂代谢紊乱大鼠模型的降血糖作用及其机制研究

目的 探讨葫芦巴籽和桑叶提取混合物(fenugreek seed and mulberry leaf extract,FSML)对胰岛素抵抗糖脂代谢紊乱模型大鼠的降血糖作用及其作用机制。方法 建立2个不同的胰岛素抵抗糖脂代谢紊乱大鼠模型,测定大鼠血糖、血脂指标,以及胰岛素受体底物蛋白1(IRS1)、葡萄糖转运蛋白4(GLUT4)、过氧化物酶体增殖物激活受体γ(PPARγ)蛋白的表达。结果 对模型1,FSML高、低剂量组均能明显降低模型大鼠的0.5h血糖值及AUC(与模型组比较,P<0.01)。对模型2,FSML高剂量组能显著降低0.5 h血糖值及AUC(与模型组比较,P<0.05)。Western blot实验结果表明,FSML高、低剂量组均能提高GLUT4和PPARγ蛋白的表达(与模型组比较,P<0.05)。结论 FSML具有降血糖作用,其作用机制可能是上调PPARγ蛋白的表达,调节胰岛素信号通路,增加GLUT4蛋白表达,从而增加细胞的葡萄糖摄取,减少外周胰岛素靶组织的胰岛素抵抗。     

钠-葡萄糖协同转运蛋白2抑制剂治疗多囊卵巢综合征的研究进展

多囊卵巢综合征(PCOS)是育龄妇女常见的异质性内分泌疾病。PCOS患者心血管疾病、糖尿病、高尿酸血症、肥胖、血脂异常及其他代谢综合征的发生风险增加。胰岛素抵抗(IR)作为PCOS代谢紊乱中心环节,其改善对于PCOS治疗意义重大。近年发现钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是增加尿糖排泄的非胰岛素依赖性降血糖药,可改善PCOS患者IR与代谢,减轻患者体质量,保护多器官,降低PCOS心血管损伤、代谢综合征、血脂异常、肾病、肝脏代谢性疾病发生风险。该文就SGLT2抑制剂通过改善IR对PCOS患者代谢及心血管功能的作用及可能的机制进行综述。     

黄连素通过调节磷脂酰肌醇-3-激酶/丝氨酸/苏氨酸激酶/葡萄糖转运蛋白4信号途径改善胰岛素抵抗的机制研究

目的研究黄连素对胰岛素抵抗细胞3T3-L1细胞磷脂酰肌醇-3-激酶/丝氨酸/苏氨酸激酶(AKT)和葡萄糖转运蛋白4(GLUT4)mRNA和蛋白表达的影响,探讨黄连素改善胰岛素抵抗的分子机制。方法将3T3-L1脂肪细胞随机分为正常对照组、胰岛素抵抗、黄连素3组,应用地塞米松诱导细胞胰岛素抵抗,黄连素组同时加入黄连素。以葡萄糖氧化酶法测定3组细胞上清液中葡萄糖消耗量,观察黄连素对脂肪细胞葡萄糖摄取的影响;应用免疫印迹技术(Western blotting)技术测定脂肪细胞AKT和GLUT4的蛋白水平变化;应用实时荧光定量PCR技术检测脂肪细胞AKT和GLUT4的mRNA表达变化。结果与正常对照组相比,胰岛素抵抗组的AKT和GLUT4 mRNA和蛋白表达明显下降(P<0.05),经黄连素干预后,AKT和GLUT4 mRNA和蛋白表达水平有一定升高,但仍显著低于正常对照组(P<0.05)。结论黄连素通过上调AKT基因和蛋白的表达进而增加GLUT4的水平,改善胰岛素抵抗状态。     

笔筒草有效组分抗2型糖尿病作用机制研究

目的研究笔筒草有效组分对2型糖尿病大鼠抗氧化作用、胰岛素抵抗的影响。方法通过腹腔注射链佐霉素联合高脂饲料喂养制备2型糖尿病大鼠模型,观察其对大鼠空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)、及葡萄糖转运蛋白4(GLUT4)的影响。结果与模型组比较,笔筒草乙醇组分及乙酸乙酯组分均可显著降低糖尿病大鼠FPG、FINS及HOMA-IR,明显升高骨骼肌GLUT4表达水平,与模型组相比,差异有统计学意义(P0.05);与乙酸乙酯组分不同之处在于,乙醇组分还能升高SOD及降低MDA含量,差异有统计学意义(P0.05)。结论笔筒草乙醇及乙酸乙酯组分降血糖机制可能与改善机体对胰岛素的敏感性,调控骨骼肌GLUT4表达水平,维持胰岛细胞的正常结构和功能密切相关,其中笔筒草乙醇组分还具有清除自由基和提高机体抗氧化能力等作用。     

葡萄糖转运蛋白1与肿瘤形成

众所周知,葡萄糖作为细胞内各种组成成分的底物是一种最重要的能量来源,组织细胞摄入葡萄糖需借助胞膜上的葡萄糖转运蛋白(GLUT)载体.近年来,有关葡萄糖转运体家族(glucose transporters,GLUTs)的分子结构、生物学活性、临床意义等方面有大量的研究报道,尤其是其在恶性肿瘤中普遍高表达,与细胞的恶性转化、增殖、侵袭能力等密切相关,是目前肿瘤研究的热点.作者着重对葡萄糖转运蛋白1(GLUT1)及其与肿瘤的关系做一简介.     

葡萄糖逆转蛋白和2型糖尿病

胰岛素抵抗和胰岛细胞功能障碍是2型糖尿病的病理生理特征,造成胰岛素抵抗的机制至今尚不清楚,可能与胰岛素的信号传导缺陷有关,尤其是葡萄糖逆转蛋白（GLUT4）的潜在缺陷,GLUT4潜在的缺陷包括：GLUT4转位受阻,GLUT4的囊泡不能与细胞膜融合,隐蔽的GLUT4不能暴露于细胞外环境,以及囊泡虽融合但GLUT4活性下降等,多种因素可以影响GLUT4的分布、含量、激活与功能。     

葛根素对胰岛素抵抗大鼠脂肪细胞葡萄糖转运蛋白4的影响

目的 :探讨葛根素对高糖高脂饮食诱导的胰岛素抵抗大鼠脂肪细胞葡萄糖转运蛋白 4 (GLUT4 )表达水平及其转位机制的影响。方法 :实验大鼠随机分为正常组、模型组和葛根素组 ,每组 10只。模型组和葛根素组大鼠喂以高糖高脂饲料 ,4周后葛根素组大鼠予以葛根素 10 0mg·kg-1·d-1腹腔注射。以Westernblot法检测各组大鼠脂肪细胞GLUT4的含量 ,定期检测实验大鼠的体质量、血甘油三酯和胆固醇、空腹血糖及血浆胰岛素水平 ,并计算胰岛素敏感指数。结果 :模型组大鼠脂肪细胞内膜GLUT4含量较正常组减少 38.72 % (P <0 .0 5 ) ,细胞外膜减少2 1.91% (P <0 .0 5 )。给予葛根素治疗 6周后 ,大鼠脂肪细胞内膜GLUT4的含量与模型组相比无明显变化 ,而细胞外膜GLUT4含量增加 2 1.4 6 % (P <0 .0 5 )。结论 :葛根素可提高胰岛素抵抗大鼠脂肪细胞GLUT4蛋白表达水平 ,且能够改善其转位机制 ,从而加强葡萄糖的摄取和利用。     

小檗碱改善2型糖尿病大鼠胰岛素抵抗与PI-3K、GLUT4蛋白相关性的研究

目的观察小檗碱对2型糖尿病大鼠骨骼肌组织磷脂酰肌醇3激酶(phosphatidylinositol-3-kinase,PI-3K)之p85亚基、葡萄糖转运子4(glucose transporter4,GLUT4)蛋白表达的影响,以探讨小檗碱改善胰岛素抵抗,防治2型糖尿病的分子机制。方法采用尾静脉注射小剂量链脲佐菌素(streptozotocin,STZ,30mg.kg-1)加高脂高热量饲料喂养的方法建立2型糖尿病大鼠模型,以小檗碱干预10wk,检测血糖和血清胰岛素,用Western blot方法检测小檗碱干预后2型糖尿病大鼠骨骼肌组织PI-3K之p85亚基、GLUT4蛋白表达水平。结果小檗碱干预的2型糖尿病大鼠骨骼肌组织PI-3K之p85亚基、GLUT4蛋白表达水平均较模型组显著增加。结论小檗碱对2型糖尿病的治疗效应可能与提高骨骼肌组织中PI-3K之p85亚基、GLUT4蛋白表达水平有关。     

过表达KLF4对棕榈酸所致L6骨骼肌细胞胰岛素抵抗的影响

目的探讨Krtippel样因子4（KLF4）过表达对大鼠L6骨骼肌细胞胰岛素抵抗的影响。方法采用棕榈酸诱导法建立大鼠IJ6骨骼肌细胞的胰岛素抵抗模型,随机分为对照组和转染组。对照组转染腺病毒空载体（Ad）,转染组转染KLF4腺病毒表达载体（Ad—KLF4）。采用Real—timePCR和Western—blot检测两组KLF4、胰岛素受体（IR）和葡萄糖转运蛋白4（GLUT4）的表达水平,采用葡萄糖氧化酶法检测两组培养液中的葡萄糖浓度。结果与对照组比较,棕榈酸诱导组对葡萄糖的摄取量显著降低（P〈0．05）,KLF4、IR、GLUT4表达显著下调（P〈0．05）。KLF4过表达可显著提高细胞对胰岛素的敏感性,并上调IR、GLUT4表达。结论过表达KLF4可导致IR、GLUT4表达上调,并改善骨骼肌细胞的胰岛素抵抗。     

GLUT4 associated proteins as therapeutic targets for diabetes

Type 2 diabetes is a complex, multifactorial disease resulting from insulin resistance in target tissues and the impairment of insulin secretion from the pancreas. One of the key metabolic actions of insulin is to control blood sugar levels by promoting glucose uptake into adipocyte and muscle cells. This is achieved by activation of a complex signal transduction cascade that stimulates the trafficking of the insulin responsive glucose transporter protein, GLUT4, from specific intracellular sites to the plasma membrane. This review is divided into two major sections. The first section gives an overview of GLUT4 trafficking and the second section focuses on the patents that have been acquired for GLUT4 associated proteins and which demonstrate potential as therapeutic targets for the treatment of diabetes. Inventions in this area include methods and agents to translocate GLUT4 to the plasma membrane independent of insulin and methods to increase the level of GLUT4 in insulin responsive cells.     

多囊卵巢综合征与胰岛素抵抗

多囊卵巢综合征（PCOS）作为一种生殖内分泌紊乱性疾病,与胰岛素抵抗（IR）关系密切,可引起空腹血糖异常、糖耐量异常、高血压、血脂紊乱等代谢综合征的表现,增加2型糖尿病、妊娠糖尿病、心血管疾病与子宫内膜癌发生的危险性。本文从流行病学、临床表现、分子机制、PCOS患者不同组织中的IR表现及药物治疗等方面综述PCOS与IR的关系。     

Putative Involvement of Endocrine Disruptors in the Alzheimer's Disease Via the Insulin-Regulated Aminopeptidase/GLUT4 Pathway

It has been well established that there is a connection between type II diabetes (DMTII) and Alzheimer''s disease (AD). In fact, the increase in AD incidence may be an emerging complication of DMTII. Both pathologies are related to estradiol (E₂) exposure; on the one hand, estrogen receptors (ER) are emerging as important modulators of glucose homeostasis through ß-pancreatic cell function; on the other hand, brain bioenergetic and cognitive deficits have been related to the down regulation of brain ERs, contributing to women ageing and AD susceptibility, both related to the reduction in estradiol levels and the deficits in brain metabolism. Here we discuss that environmental contaminants with estrogenic capacity such as bisphenol A (BPA) could develop pharmacological effects similar to those of E₂, which could affect ß-pancreatic cell function by increasing the biosynthesis of glucose-induced insulin after extranuclear ER binding. BPA-induced hyperinsulinemia would promote the translocation of glucose transporter 4 (GLUT4), which is located next to insulin-regulated aminopeptidase (IRAP) in intracellular vesicles. In insulin-responsive tissues, IRAP and GLUT 4 are routed together to the cell surface after insulin stimulation. IRAP is also the angiotensin IV (AngIV) receptor, and AngIV associates the brain renin-angiotensin system (bRAS) with AD, since AngIV is related to learning, memory, emotional responses, and processing of sensory information not only through its inhibitory effect on IRAP but also through the stimulation of glucose uptake by increasing the presence of IRAP/GLUT4 at the cell surface. Thus, the IRAP/GLUT4 pathway is an emerging target for pharmacological intervention against AD.     

Morin alleviates fructose-induced metabolic syndrome in rats via ameliorating oxidative stress,inflammatory and fibrotic markers

Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.     

Toona sinensis Roem (Meliaceae) leaf extract alleviates hyperglycemia via altering adipose glucose transporter 4

In this study we tested the effects of Toona sinensis leaf extracted with water (TSL1) on alloxan-induced (50 mg/kgBwt, i.v.) diabetic Long-Even rats. Diabetic rats given TS leaf with water (TSL1), with 50% alcohol (TSL3) or with H2O extract (TSL5) showed lower levels of plasma glucose. Normal rats given Glibenclamide (GC) had lower levels of plasma glucose, but TSL1 administration showed no significant effect on plasma glucose. By contrast, TSL1 or GC given to alloxan-induced diabetic rats showed a 40% reduction in plasma glucose compared to diabetic rats. Diabetic rats had lower levels of insulin. Interestingly, TSL1 or GC given to diabetic rats showed improvements in plasma insulin levels. Diabetic rats had lower expressions of glucose transporter 4 (GLUT4) mRNA (RT-PCR) and GLUT4 protein (Western blot) in brown and white adipose tissues; in contrast, diabetic rats given TSL1 or GC showed a significant increase in both GLUT4 mRNA and protein levels. Moreover, the expressions of GLUT4 mRNA in red and white muscles were not significantly different among diabetic rats, diabetic rats given TSL1 or GC, and the normal rats. Compared to diabetic rats, diabetic rats given TSL1 or GC had lower levels of GLUT4 protein in white muscle but not in red muscle. Conclusively, T. sinensis Roem (Meliaceae) leaf possesses the hypoglycemia effect underlying an increment of insulin to mediate the adipose glucose transporter 4 mechanism.     

Glucose transporter and Na+/glucose cotransporter as molecular targets of anti-diabetic drugs

Glucose transporters, or membrane proteins, which incorporate glucose into the cell, can be divided into two groups: the facilitative type glucose transporter (GLUT), and the sodium/glucose cotransporter (SGLT). Among the GLUT family isoforms, GLUT4 is particularly important for maintaining glucose metabolism homeostasis since it is involved in insulin or exercise-induced glucose transport into muscle and adipose tissues via movement from intracellular sites to the plasma membrane in response to stimulation. Thus, agents which induce GLUT4 translocation or improve insulin sensitivity, involved in this insulin-induced step, hold the promise of being potent anti-diabetic drugs. On the other hand, SGLT is expressed specifically in the intestines and kidneys. Oral administration of a SGLT inhibitor, T-1095, lowers the blood glucose concentration via excretion of glucose in the urine, due to suppression of renal SGLT function. In addition to this direct blood glucose lowering effect, T-1095 has been shown to restore impaired insulin secretion from pancreatic beta-cells, as well as to improve insulin resistance in muscle and liver. Thus, this SGLT inhibitor is regarded as a novel and promising agent for the treatment of diabetes mellitus.     

基于PI3K/AKT通路探究柚皮素改善多囊卵巢综合征大鼠胰岛素抵抗的作用机制

目的　基于磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）通路,初步探究柚皮素防治大鼠多囊卵巢综合征（PCOS）胰岛素抵抗的分子机制。方法　SD大鼠颈背部每日皮下注射脱氢表雄酮建立PCOS模型,将造模成功的大鼠采用随机数字表法分为模型组、柚皮素组、PI3K抑制剂组、柚皮素+PI3K抑制剂组,每组15只;相同时间段取SD大鼠15只,于颈背部皮下注射油剂2 mL/kg,作为正常对照组。检测各组大鼠血糖、胰岛素、血脂、生殖激素水平,计算胰岛素抵抗指数;HE染色观察卵巢形态;免疫组化法检测磷酸化PI3K（p-PI3K）阳性表达;Western blot法检测PI3K/AKT通路磷酸化蛋白及通路相关蛋白胰岛素受体底物-1（IRS-1）、糖原合成酶激酶-3β（GSK-3β）、葡萄糖转运蛋白因子-4（GLUT4）、人第10号染色体上磷酸酶和张力蛋白同源缺失基因（PTEN）蛋白表达。结果　与正常对照组相比,模型组大鼠卵巢组织出现卵泡囊性扩张、黄体数量及颗粒细胞层减少、闭锁卵泡增多等病理损伤症状,血脂、血糖、胰岛素水平升高,胰岛素抵抗增加,生殖激素分泌紊乱,PI3K/AKT通路磷酸化蛋白及通路相关蛋白IRS-1、GSK-3β磷酸化蛋白表达、GLUT4蛋白表达降低,PTEN蛋白表达升高（P＜0.05）。柚皮素可减轻卵泡囊性扩张等病理损伤,促进PI3K/AKT通路及通路相关蛋白IRS-1、GSK-3β磷酸化蛋白及GLUT4蛋白表达,改善生殖激素分泌紊乱现象,减轻胰岛素抵抗,降低血糖、血脂水平及PTEN蛋白表达（P＜0.05）。PI3K抑制剂可减弱柚皮素的上述作用（P＜0.05）。结论　柚皮素可通过促进PI3K/AKT通路活化,降低血糖、血脂水平及胰岛素抵抗,改善PCOS大鼠生殖激素紊乱及卵巢多囊改变。     

Role of SNARE's in the GLUT4 translocation response to insulin in adipose cells and muscle

Insulin stimulates glucose transport in skeletal muscle, heart, and adipose tissue by promoting the appearance of GLUT4, the major glucose transporter isoform present in these tissues, on the cell surface. This is achieved by differentially modulating GLUT4 exocytosis and endocytosis, between a specialized intracellular compartment and the plasma membrane. Ligands which activate the heterotrimeric GTP-binding proteins Gs and Gi appear to modulate insulin-stimulated glucose transport through effects on the fusion of docked GLUT4-containing vesicles with the plasma membrane. In insulin resistance states, reduced cellular GLUT4 levels in adipose cells fully account for the decreased glucose transport response to insulin in these cells. In contrast, although insulin-stimulated GLUT4 translocation is also impaired in muscle, total cellular levels of GLUT4 are not altered. The defect in muscle has been attributed to a GLUT4 trafficking problem and thus studies of this mechanism could provide clues as to the nature of the impairment. The movement of GLUT4-containing vesicles from an intracellular storage site to the plasma membrane and the fusion of docked GLUT4-containing vesicles with the plasma membrane are conceptually similar to some secretory processes. A general hypothesis called the SNARE hypothesis (soluble NSF attachment protein receptors where NSF stands for N-ethylmaleimide-sensitive fusion protein) postulates that the specificity of secretory vesicle targeting is generated by complexes that form between membrane proteins on the transport vesicle (v-SNARE's) and membrane proteins located on the target membrane (t-SNARE's). Several v- and t-SNARE's have been identified in adipose cells and muscle. VAMP2 and VAMP3/cellubrevin (v-SNARE's) have been shown to interact with the t-SNARE's syntaxin 4 and SNAP-23. The cytosolic protein NSF has the characteristic of binding to the v-/t-SNARE complex through its interaction with alpha-SNAP, another soluble factor. Furthermore, recent studies have demonstrated that VAMP2/3, syntaxin 4, SNAP-23, and NSF are functionally involved in insulin-stimulated GLUT4 translocation in adipose cells and thus are likely to be involved in the Gs- and Gi-mediated modulation of the glucose transport response to insulin as well. This review summarizes recent advances on the normal mechanism of GLUT4 translocation and discusses how this process could be affected in insulin resistant states such as type II diabetes.     

In silico and in vivo analysis to identify the antidiabetic activity of beta sitosterol in adipose tissue of high fat diet and sucrose induced type-2 diabetic experimental rats

Adipose tissue is the primary site of storage for excess energy as triglyceride and it helps in synthesizing a number of biologically active compounds that regulate metabolic homeostasis. Consumption of high dietary fat increases stored fat mass and is considered as a main risk factor for metabolic diseases. Beta-sitosterol (β-sitosterol) is a plant sterol. It has the similar chemical structure like cholesterol. Clinical and experimental studies have shown that β-sitosterol has anti-diabetic, hypolipidemic, anti-cancer, anti-arthritic, and hepatoprotective role. However, effect of β-sitosterol on insulin signaling molecules and glucose oxidation has not been explored. Hence in the present study we aimed to discover the protective role of β-sitosterol on the expression of insulin signaling molecules in the adipose tissue of high-fat diet and sucrose-induced type-2 diabetic experimental rats. Effect dose of β-sitosterol (20?mg/kg b.wt, orally for 30?days) was given to high fat diet and sucrose-induced type-2 diabetic rats to study its anti-diabetic activity. Results of the study showed that the treatment with β-sitosterol to diabetes-induced rats normalized the altered levels of blood glucose, serum insulin and testosterone, lipid profile, oxidative stress markers, antioxidant enzymes, insulin receptor (IR), and glucose transporter 4 (GLUT4) proteins. Our present findings indicate that β-sitosterol improves glycemic control through activation of IR and GLUT4 in the adipose tissue of high fat and sucrose-induced type-2 diabetic rats. Insilico analysis also coincides with invivo results. Hence it is very clear that β-sitosterol can act as potent antidiabetic agent.     

Effect of Lycium barbarum polysaccharide on the improvement of insulin resistance in NIDDM rats

Lycium barbarum is one of the traditional oriental medicines. It has been reported to reduce blood glucose levels. In this study, the effect of Lycium barbarum polysaccharide (LBP) on the improvement of insulin resistance and lipid profile was studied in rats, a model for non-insulin dependent diabetes mellitus (NIDDM). The rats were divided into three groups: control, NIDDM control, and NIDDM+LBP. Diabetes model groups were made by feeding high-fat diet and subjecting to i.p. streptozotocin (50 mg/kg). LBP treatment for 3 weeks resulted in a significant decrease in the concentration of plasma triglyceride and weight in NIDDM rats. Furthermore, LBP markedly decreased the plasma cholesterol levels and fasting plasma insulin levels, and the postprandial glucose level at 30 min during oral glucose tolerance test and significantly increased the Insulin Sensitive Index in NIDDM rats. In the present study, we have tested that LBP can alleviate insulin resistance and the effect of LBP is associated with increasing cell-surface level of glucose transporter 4 (GLUT4) in skeletal muscle of NIDDM rats. Under insulin stimulus, GLUT4 content in plasma membrane in NIDDM control rats was significantly lower than that of control (p<0.01), and GLUT4 content in the plasma membrane in NIDDM+LBP rats was higher than that of NIDDM control rats (p<0.01). In conclusion, LBP can ameliorate insulin resistance, and the mechanism may be involved in increasing cell-surface level of GLUT4, improving GLUT4 trafficking and intracellular insulin signaling.