高含量DHA/EPA甘油三酯对脂质代谢相关酶活力的影响

目的研究高含量DHA/EPA甘油三酯对脂肪肝模型大鼠肝脏脂质代谢相关酶活力的影响。方法采用1%乳清酸饲喂法建立脂肪肝大鼠模型。灌胃高含量DHA/EPA甘油三酯20d后,检测大鼠血清和肝脏总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)含量以及肝脏脂肪合成和分解相关酶活力。结果高含量DHA/EPA甘油三酯可预防大鼠血清和肝脏脂质含量升高(P<0.05,P<0.01),显著提高肉碱棕榈酰转移酶(car...     

葛根素对胰岛素抵抗大鼠脂肪组织中糖原合成酶激酶3β表达的影响

目的探讨葛根素对高脂饮食诱导的胰岛素抵抗大鼠脂肪组织中糖原合成酶激酶3β(GSK-3β)表达的影响。方法30只SPF级雄性Wister大鼠随机分为2组,正常对照组10只,常规饲料喂养,模型组20只,高脂饲料喂养;4周后模型形成,模型组随机分为2组(胰岛素抵抗组、葛根素干预组,每组10只),继以高脂饲料喂养,葛根素干预组同时给予葛根素注射液100mg·kg-1·d-1腹腔注射。干预6周后,用Western-blot方法检测各组大鼠附睾脂肪组织中GSK-3β的表达,分析对比各组的表达差异;定期检测大鼠体重、空腹血糖及血浆胰岛素、血甘油三酯和胆固醇,并计算胰岛素敏感指数。结果高脂饲料喂养4周后,与正常对照组比较,模型组大鼠体重(BW)、空腹血糖(FPG)、胰岛素(FINS)、胆固醇(TC)、甘油三酯(TG)显著升高(P<0.05或P<0.01),胰岛素敏感指数ISI显著下降(P<0.01),胰岛素抵抗模型诱导成功;葛根素干预6周后,与胰岛素抵抗组大鼠比较,脂肪组织中GSK-3β的表达显著下降(P<0.05),和正常对照组比较,无显著差异。结论葛根素显著下调脂肪组织GSK-3β的表达,并且可能参与其改善胰岛素抵抗的机制。     

高含量EPA/DHA甘油三酯型鱼油对小鼠的免疫调节作用

目的采用免疫功能低下小鼠模型研究高含量EPA/DHA甘油三酯型鱼油的免疫调节作用。方法Balb/c小鼠,随机分为正常对照组、模型对照组、阳性对照组、乙酯型鱼油组、低含量EPA/DHA甘油三酯型鱼油组和高含量EPA/DHA甘油三酯型鱼油低、高剂量组,每组10只。剂量组小鼠分别灌胃不同种类的鱼油,阳性对照组灌胃左旋咪唑(20mg·kg-1),正常和模型对照组灌胃生理盐水,连续28d。除正常对照组外,其余各组小鼠均于首次给药第21d,连续7d皮下注射氢化可的松(19mg·kg-1),建立免疫功能低下小鼠模型。于末次给药后,分别测定小鼠的各免疫指标。结果高含量EPA/DHA甘油三酯型鱼油可显著改善模型小鼠的血清溶血素水平及抗体生成细胞数,提高迟发性变态反应水平和脾淋巴细胞转化能力,促进腹腔巨噬细胞的吞噬能力和碳廓清能力,提高IFN-γ/IL-4比值,且效果优于低含量EPA/DHA甘油三酯型鱼油和乙酯型鱼油。结论高含量EPA/DHA甘油三酯型可显著改善免疫低下模型小鼠的免疫调节功能,其免疫调节作用可能与其甘油三酯含量及EPA/DHA含量相关。     

葛根素对胰岛素抵抗大鼠肝脏中GSK-3表达的影响

目的:观察高糖高脂饮食诱导的胰岛素抵抗大鼠通过葛根素治疗后肝脏中GSK-3的表达。方法:将30只Wistar大鼠随机分为正常组、模型组和葛根素组,每组各10只。3组均以基础饲料喂养一周,然后正常组仍以基础饲料喂养,模型组和葛根素组改喂高糖高脂饮食,4周后葛根素组大鼠给予100mg.kg-1.d-1葛根素腹腔注射,连续6周,待造模成功后,用Western-blot法检测各组大鼠肝脏中GSK-3的表达,并分别在1、51、1周定期检测TG(总甘油三酯),TC(总胆固醇),FBG(空腹血糖),FINS(空腹胰岛素)并计算ISI(胰岛素敏感指数)和HOMA-IR(胰岛素抵抗指数)。结果:模型组大鼠肝脏中GSK-3的表达较正常组增高129.4%(P<0.01),用葛根素治疗后,大鼠肝脏中GSK-3的表达较模型组减少14.6%。结论:葛根素可降低胰岛素抵抗大鼠肝脏中GSK-3的表达。     

中药降糖复方水提取物对KK-Ay糖尿病小鼠骨骼肌糖代谢PI3K/Akt信号通路的影响

目的 研究中药降糖复方水提取物（WEJTD）对自发性2型糖尿病（T2DM）模型KK-Ay小鼠骨骼肌糖代谢PI3K/Akt信号通路的影响。方法 将KK-Ay小鼠按随机数法随机分为5组：模型组、盐酸二甲双胍（MH,250 mg/kg）组和WEJTD低、中、高剂量（2、4、8 g/kg）组,C57BL/6J小鼠作为对照组,每天ig给药1次,共12周,对照组和模型组ig等体积蒸馏水。给药12周后,取小鼠血清,ELISA试剂盒法检测胰岛素水平;Trizol法提取肌肉组织中的RNA,荧光实时定量PCR（qRT-PCR）检测磷脂酰肌醇激酶-3（PI3K）、蛋白激酶B（Akt）、葡萄糖转运蛋白-4（GLUT-4）、糖原合成酶激酶-3β（GSK-3β）、糖原合成酶（GS）、胰岛素受体底物（IRS-1）mRNA水平。结果 与模型组比较,WEJTD高、中剂量显著上调小鼠血清胰岛素水平、骨骼肌中IRS-1 mRNA水平（P<0.05、0.001）;高、中、低剂量均显著下调骨骼肌中GSK-3β mRNA水平,显著上调PI3K、Akt、GLUT-4、GS mRNA水平（P<0.05、0.01、0.001）。结论 中药降糖复方通过上调PI3K/Akt信号通路,减少糖原沉积,刺激骨骼肌中葡萄糖转运。     

胰岛素抵抗骨骼肌细胞中P-Ser473PKB及糖原合成酶-3表达

目的探讨棕榈酸(PA)诱导的胰岛素抵抗(IR)骨骼肌细胞中P-Ser473PKB及糖原合成酶(GSK)-3的表达。方法培养大鼠骨骼肌细胞,免疫荧光鉴定原代大鼠骨骼肌细胞;设立对照组、PA组(0.6mmol/L PA),在细胞培养6、122、4 h后,胰岛素刺激15 min,葡萄糖氧化酶-过氧化物酶偶联(GOD-POD)法测定培养液中葡萄糖的浓度;Western blot检测P-Ser473PKB及P-Ser21/9GSK-3α/β的蛋白表达。结果 90%以上的肌细胞-αsarcometric actin单克隆抗体染色呈阳性,证明培养的为骨骼肌细胞;培养24 h后,PA组培养液中葡萄糖浓度高于对照组,P-Ser473PKB蛋白水平低于对照组,而P-Ser21/9GSK-3α/β高于对照组(P值均<0.05)。结论 PA作用下,胰岛素刺激的骨骼肌细胞对葡萄糖的处理能力下降,即PA可诱导骨骼肌细胞产生胰岛素抵抗,其机制可能与P-Ser473PKB蛋白表达下调,P-Ser21/9GSK-3α/β表达增加有关。     

可溶性白细胞分化抗原14和可溶性肿瘤坏死因子受体-P55治疗严重烫伤小鼠实验研究

目的:观察可溶性白细胞分化抗原14(sCD14)和可溶性肿瘤坏死因子受体-P55(sTNFR-P55)对严重烫伤模型小鼠炎症反应、胰岛素抵抗和胰岛素分泌的治疗效果。方法:模型小鼠单独及联合静脉注射sCD14和sTNFR-P55,观察不同治疗组以及治疗对照组(模型组)、正常对照组的死亡率、外周血白细胞(WBC)总数、稳态模式胰岛素抵抗(HOMA-IR)指数和胰岛素分泌(HOMA-β)指数以及空腹血糖和乳酸含量变化。结果:sCD14和sTNFR-P55联合组小鼠死亡率明显低于治疗对照组(P<0.05);联合组及单一治疗组WBC总数、HOMA-IR指数、空腹血糖和乳酸含量均明显低于治疗对照组,且联合组低于单一治疗组;但HOMA-β指数治疗组明显高于治疗对照组(P<0.01),且联合组高于单一治疗组(P<0.01)。结论:静脉注射sCD14和sTNFR-P55能够有效改善创伤炎症反应、胰岛素抵抗和胰岛β细胞功能障碍,降低创伤模型小鼠病死率,且联合治疗效果优于单一治疗。     

牛大力多糖对糖尿病小鼠降血糖作用的研究

目的研究牛大力多糖对糖尿病模型小鼠的降血糖作用。方法采用链脲佐菌素(STZ)诱导糖尿病小鼠模型,使用低、中、高剂量牛大力多糖对模型小鼠进行干预,分别比较牛大力多糖干预组、模型组及对照组小鼠空腹血糖(FBG)、空腹胰岛素(FINS)及肝糖原含量。结果牛大力多糖可以显著降低STZ诱导的糖尿病小鼠FBG水平(P <0.01),提高模型小鼠FINS水平和肝糖原含量(P <0.01)。结论牛大力多糖可显著降低糖尿病小鼠血糖水平,其作用机制可能与增加胰岛素分泌,促进糖原合成有关。     

2型糖尿病病程与胰岛β细胞功能的演变

目的:研究2型糖尿病进展过程中胰岛β细胞功能和胰岛素敏感性的变化特点。方法:将113例2型糖尿病患者按照糖尿病病程分3组:A组(<5年)、B组(5～9年)和C组(≥10年)。所有患者均做100 g标准馒头餐试验,测定血糖及胰岛素水平。结果:(1)C组与A组比较空腹血糖水平显著升高(P<0.01)。B组和C组负荷后1,2,3 h血糖均高于A组(P<0.05)。C组负荷后3 h血糖较B组有显著升高(P<0.05)。(2)C组负荷后1 h和2h胰岛素分泌水平降低(P<0.05),胰岛β细胞分泌功能(HOMA-β)显著下降(P<0.01),但胰岛素分泌曲线下面积(AUC)仅与A组有显著性差异(P<0.001)。(3)负荷后胰岛素与基础胰岛素比值(INS1～3/INS0)的特点为C组INS1/INS0和INS2/INS0比值减低(P<0.05)。此外,相关性分析发现,INS1/INS0和INS2/INS0比值分别与空腹血糖、β细胞功能显著相关(P<0.05或P<0.01)。结论:2型糖尿病患者胰岛β细胞继续发生变化,C组胰岛β细胞分泌胰岛素的水平和反应性显著下降。     

新诊断2型糖尿病血清Apelin及TNF-a水平与胰岛素抵抗的相关性研究

目的:探讨新诊断2型糖尿病(type2diabetes mellitus,T2DM)患者血清Apelin及肿瘤坏死因-a(tumor necrosisfactor,TNF-a)水平与胰岛素抵抗(insulin resistance,IR)的相关性。方法:收集未经治疗的新诊断T2DM患者(T2DM组,n=60),同期健康体检者为正常对照组(NC组,n=30)。检测血清Apelin、TNF-a、甘油三酯(TG)、胆固醇(CHOL)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、空腹血糖(FBG)、空腹胰岛素(FIN)、空腹C肽(C-P)、糖化血红蛋白(HbA1c)水平及体质量指数(BMI),以稳态模型计算胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、胰岛素敏感性(ISI)。结果:新诊断T2DM患者Apelin、TNF-a水平均显著高于NC组(P<0.05),且与HOMA-IR、BMI、FBG、TG、HbA1c呈正相关(P<0.01),与ISI、HOMA-β、HDL呈负相关(P<0.01);且Apelin与TNF-a呈正相关(P<0.01)。Apelin为影响TNF-a最显著因素,常数项为0.03,(β=0.439,P<0.01)。结论:新诊断T2DM患者血清Apelin、TNF-a水平升高,且二者成正相关。血清Apelin与TNF-a水平的高表达与胰岛素抵抗相关。     

Fucoidan from sea cucumber may improve hepatic inflammatory response and insulin resistance in mice

Nutrition excess-induced inflammation positively contributed to insulin resistance. Fucoidan from sea cucumber can increase glucose translocation in skeletal muscle. However, its effects on inflammation-associated insulin resistance are not understood. We investigated fucoidan from Isostichopus badionotus (Ib-FUC)-alleviated inflammatory response and signaling as well as -improved insulin resistance in the liver of obesity mice. The results showed that Ib-FUC reduced body weight and glucose levels, increased insulin sensitivity, and inhibited serum lipid concentrations. Meanwhile, Hepatic glycogen synthesis was promoted by Ib-FUC via activation of the PI3K/PKB/GSK-3β signaling and regulation of glucose metabolism-related enzymatic activities. Ib-FUC regulated serum inflammatory cytokines and their mRNA expression in the liver. Ib-FUC-induced inactivation of the JNK and IKKβ/NFκB pathways was involved in the activation of insulin signal cascade and inflammatory factor production. These findings suggested that Ib-FUC supplementary-induced alleviation of inflammatory response could be a mechanism responsible for its beneficial effects against hepatic insulin resistance.     

Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventive effect of Arachidonic acid on insulin resistance

Elevated plasma levels of free fatty acids (FFAs) may contribute to insulin resistance (IR) that is characteristic of type 2 diabetes mellitus. In this study, we investigated the effects of two fatty acids, palmitate (PA) and arachidonic acid (AA) on glycogenesis under insulin signaling in HepG2cells, a transformed hepatic carcinoma cell line. In the presence of 200 μmol of palmitate, insulin (10⁻⁷ mol/L) stimulation of glycogenesis was inhibited, as evidenced by increased glucose in the medium and decreased intracellular glycogen. Wortmannin (WM), a specific inhibitor of PI3K, dramatically decreased the amount of intracellular glycogen in cells without PA incubation. However, glycogen in PA treated cells was not significantly changed by WM, indicating that PA may also act on PI3K. Interestingly, AA restored the effects of WM inhibition on glycogenesis in PA cells. Western blot analysis demonstrated that PA in the absence of WM increased phosphorylated glycogen synthase (inactive form of GS) and decreased phosphorylated protein kinase B (active form of PKB), causing a reduction of intracellular glycogen. AA, however, reversed the effects of PA on GS and PKB. Furthermore, inhibition of protein kinase C (PKC) by a specific inhibitor chelerythrine chloride (CC) abolished the inhibitory effect of PA on glycogen synthesis by decreasing phosphorylated GS and increasing phosphorylated PKB. However, the effect of CC in the presence of PA disappeared when AA was also present. Our results suggest that there is a disruption of the insulin signaling pathway between PKB and GS when the cells were exposed to PA, contributing to IR. PA may also interrupt the PKC signaling pathway. In contrast, AA could rescue glycogenesis impaired by PA.     

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。     

白藜芦醇衍生物改善2型糖尿病大鼠血糖及胰岛素抵抗作用的研究

目的探讨白藜芦醇衍生物BTM-0512对2型糖尿病大鼠血糖及胰岛素抵抗作用的影响。方法单次腹腔注射链脲佐菌素（STZ,35mg·kg^-1）结合高脂饮食建立2型糖尿病大鼠模型。糖尿病大鼠分为3组（模型组、BTM-0512低剂量组、BTM-0512高剂量组）,药物灌胃3周。检测空腹血糖（FBG）、糖基化血红蛋白（HblAC）、空腹血清胰岛素（Fins）和口服糖耐量（OGTT）;计算HOME．IR、胰岛素敏感指数（1AD、胰岛素分泌指数（IS）,以此评价胰岛素抵抗（IR）。结果BTM-0512能剂量依赖性降低2型糖尿病大鼠FBG和HblAC,改善HOME．IR和IAI,但对OGTT与IS没有影响。结论BTM0512可以降低2型糖尿病大鼠血糖并改善IR。     

不同时点糖代谢异常孕妇胰岛素抵抗与β细胞功能的研究

目的:研究不同糖耐量状态人群胰岛素抵抗(IR)和β细胞分泌功能的区别.方法:收集孕前体质指数正常,无孕前合并症及妊娠期并发症,50 g葡萄糖筛查试验阳性患者504例,行口服葡萄糖耐量试验(OGTT)及胰岛素释放试验.依美国糖尿病协会(ADA)诊断标准分组,计算并比较各组胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)以及反映葡萄糖刺激后胰岛素最大分泌功能的△PI/△PG.结果:不同时点糖代谢异常患者胰岛素释放特征不同,组间比较差异有统计学意义.与正常组(NGT)相比,葡萄糖耐量受损(GIGT)0、1、2及妊娠期糖尿病(GDM)组HOMA-IR均有不同程度增加,HOMA-β和△PI/△PG有不同程度下降,差异有统计学意义(P＜0.01),GIGT3与GIGT1、GDM差异有统计学意义(P＜0.05),GIGT0与GDM组△PI/△PG差异有统计学意义(P＜0,01).结论:妊娠期糖代谢异常患者不仅存在IR,还有β细胞功能的受损,GIGT的不同时点血糖异常者具有不同的代谢特异性,GIGT0、GIGT1与GDM相近似,GIGT3与NGT近似.     

糖尿病治疗新靶点糖原合成酶激酶-3抑制剂的研究进展

糖原合成酶激酶-3(glycogen synthase kinase-3，GSK-3)属丝氨酸/苏氨酸类激酶，最早是作为一种能磷酸化并抑制糖原合成酶活性的蛋白激酶而被发现的。已发现在某些人类疾病中GSK-3的活性异常升高，如糖尿病、阿尔茨海默病及其他一些神经退行性疾病。现已找到了一些小分子GSK-3抑制剂主要是通过使GSK-3的丝氨酸位点磷酸化，从而抑制其活性。GSK-3活性被抑制后，能影响胰岛素信号传导、葡萄糖代谢及糖原的合成。因此开发GSK-3抑制剂已成为研究抗糖尿病药物的一个新思路。本文主要介绍GSK-3与糖尿病的联系及近年来GSK-3抑制剂在抗糖尿病作用方面的研究进展。     

恒顺降糖胶囊对2型糖尿病大鼠胰岛素抵抗的影响

目的观察恒顺降糖胶囊(Hengshun Jiangtang capsules,HS)对2型糖尿病大鼠胰岛素抵抗的影响。方法对连续10d灌胃给予脂肪乳的大鼠腹腔注射四氧嘧啶,72h后血糖值≥16.7mmol·L-1者为2型糖尿病大鼠模型;给药28d,观察HS对空腹血糖(FBG)、糖耐量(OGTT)、空腹血清胰岛素(FINS)、胰岛素耐量(ITT)和胰岛素抵抗指数(Homa-IR)的影响。结果HS能改善2型糖尿病大鼠的OGTT和ITT,降低FGB,FINS和Homa-IR。结论HS明显降低2型糖尿病大鼠的胰岛素血症,改善其对胰岛素的抵抗。     

Potentiation of neuronal insulin signaling and glucose uptake by resveratrol: the involvement of AMPK

Resveratrol (RSV), a polyphenolic phytoestrogen, has been shown to activate the serine/threonine kinase 5'-adenosine monophosphate-activated protein kinase (AMPK) and to stimulate insulin signaling and glucose uptake in skeletal muscle cells. A direct effect of RSV on neuronal insulin signaling, however, has not been demonstrated. Here, we report that RSV stimulates glucose uptake and potentiates insulin signaling in Neuro-2A (N2A) cells, which is characterized by the increased phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). Furthermore, RSV activates AMPK in N2A cells, which can be prevented using a specific pharmacological inhibitor, Compound C. Compound C abrogates RSV-induced Akt and GSK-3β phosphorylation and glucose uptake. Thus, we demonstrate that RSV potentiates insulin signaling and glucose uptake via AMPK activation in neuronal cells.     

METABOLIC EFFECTS OF THIOCTIC ACID IN RODENT MODELS OF INSULIN RESISTANCE AND DIABETES

1. The antioxidant thioctic acid (TA) has been used in the treatment of diabetic neuropathy and recent studies have suggested that TA also has pancreatic and peripheral effects that improve glucose transport and metabolism. In the present study, the metabolic effects of TA were evaluated in rodent models of insulin resistance (fructose-fed Sprague-Dawley rat) and insulin deficiency (streptozotocin (STZ)-induced diabetic rat). Oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in conscious rats after treatment with 50 mg/kg per day TA or vehicle for 5 days. 2. Fructose feeding for 7 days induced insulin resistance and impaired glucose tolerance and hypertriglycerideaemia. Treatment of fructose-fed rats with TA had no significant effect on fasting or stimulated glucose levels or on fasting triglyceride concentrations (e.g. the area under the curve for glucose (AUC_glu) following OGTT was 1233 ± 67 and 1284 ± 59 in fructose-fed rats treated with either TA (n= 12) or vehicle (n= 12), respectively). Similarly, TA had no significant effect on IVGTT profiles in fructose-induced insulin resistance. 3. Low-dose STZ (80 mg/kg, i.p, over 2 days) induced hyper-glycaemia, but TA had no significant glucose-lowering effects in STZ-diabetic rats (AUC_glu (OGTT) following oral administration was 5507 ± 27 and 5450 ± 27 in TA (n= 12) and vehicle-treated (n= 12) rats, respectively). Nor did pretreatment with TA affect the diabetogenic response to STZ. 4. In contrast with previous in vitro studies reporting favourable metabolic effects of TA, the present study shows that after short-term oral therapy there are no significant improvements in glucose tolerance in rodent models of insulin resistance and insulin deficiency. Thioctic acid is unlikely to be of therapeutic benefit as an anti-diabetic drug in clinical practice.