氧化应激在实验性糖尿病神经病变中的作用

目的：探讨氧化应激在糖尿病神经病变发生发展中的作用。方法：用链脲佐菌素诱导糖尿病大鼠模型。测定糖尿病不同时期坐骨神经中丙二醛（MDA）的水平、总超氧化物歧化酶（SOD）及Na＋-K＋依赖式ATP酶的活性。分析糖尿病大鼠坐骨神经中MDA水平与Na＋-K＋依赖式ATP酶活性的相关性。光镜下观察糖尿病不同时期坐骨神经的病理改变。结果：糖尿病1个月,3个月和6个月时MDA水平与对照组相比显著增高。糖尿病1个月时总SOD活性与对照组相比明显增高,3个月和6个月时活性明显降低。糖尿病3个月和6个月时Na＋-K＋依赖式ATP酶活性与对照组相比显著降低。糖尿病大鼠坐骨神经中MDA水平与Na＋-K＋依赖式ATP酶活性的相关性分析表明,两者呈显著的负相关。病理组织学观察表明,糖尿病3个月时坐骨神经出现病理改变,随着糖尿病病程的延长,病理改变加重。结论：糖尿病早期未出现神经病变时坐骨神经已存在明显的氧化应激,并且在神经病变发生后仍存在。氧化应激与坐骨神经中Na＋-K＋依赖式ATP酶的活性降低有关。因此,氧化应激在糖尿病神经病变的发生发展中起重要作用。     

白藜芦醇甙对糖尿病小鼠心肌损伤的保护作用及机制研究

目的:探讨白藜芦醇甙对小鼠小鼠心肌损伤的影响及其可能的调控机制。方法:采用腹腔注射链脲霉素的方法建立1型糖尿病小鼠模型模型,随机将雄性C57/BL6J的正常小鼠和糖尿病小鼠分为3组(每组18只):对照组、糖尿病组、糖尿病+白藜芦醇甙组。其中糖尿病+白藜芦醇甙组给予白藜芦醇甙7.5 mg/kg/d腹腔注射治疗,对照组和糖尿病组给予同体积盐水腹腔注射。药物治疗12周后,小动物心脏超声检测小鼠的心功能;天狼星红染色观察胶原变化并进一步计算胶原容积分数(collagen volume fraction,CVF);柠檬酸合酶检测试剂盒和ATP生物荧光试剂盒分别检测检测心肌柠檬酸合酶活性和ATP含量;Western blot检测Sirt3和p-AMPK的蛋白表达情况。结果:与对照组相比,糖尿病组LVEDD和LVESD均明显增加(4.823±0.103 mm和3.701±0.121 mm,P0.05),LVEF和LVFS值均明显降低(37.121±4.298%和21.023±2.187%,P0.05),CVF显著增高(20.102±1.155%,P0.05),心肌柠檬酸合酶活性和ATP含量显著降低(5.267±0.202 nmol/g和105±7.638 U/g,P0.05),Sirt3和p-AMPK蛋白表达显著降低(P0.05);与糖尿病组相比,糖尿病+白藜芦醇甙组LVEDD和LVESD均显著降低(4.354±0.113 mm和3.056±0.130 mm,P0.05),LVFS和LVEF值均显著增加(58.435±8.143%和29.071±2.232%,P0.05),CVF显著降低(10.343±0.882%,P0.05),心肌柠檬酸合酶活性和ATP含量显著增加(6.233±0.176 nmol/g和132.7±5.774 U/g,P0.05),Sirt3和p-AMPK蛋白表达显著增加(P0.05)。结论:白藜芦醇甙可改善糖尿病小鼠心肌损伤,其机制可能与白藜芦醇甙激活Sirt3/AMPK信号通路有关。     

外源ATP对油菜幼苗耐寒性的影响

以“陇油7号”油菜为实验材料,研究了外源ATP对油菜幼苗耐寒性的影响。结果表明:与单独低温胁迫相比,外源ATP预处理再进行低温胁迫后,油菜幼苗MDA含量、O₂^-.含量均显著降低,而叶绿素含量、抗氧化酶活性(SOD、POD、CAT、APX)和RBOHD、RBOHF、CPK4、CPK5基因表达均增加;与外源ATP+低温相比,EGTA+外源ATP+低温处理下,MDA含量显著增加,总叶绿素含量、T-AOC酶活性、RBOHD、RBOHF基因表达均显著下降,DMTU+外源ATP+低温处理下,MDA含量显著增加,总叶绿素含量、Ca²⁺-ATPase酶活性、CPK4、CPK5基因表达均下降,表明外源ATP通过Ca²⁺和H₂O₂依赖性机制影响油菜幼苗的耐寒性。     

Triton X—100加KI对燕麦根细胞质膜ATP酶的溶解

在酸性条件下,1％ Triton X—100加 0.25mol/L KI能有效地溶解燕麦根细胞质膜ATP酶。溶解的ATP酶水解ATP的最适pH在6.5左右,酶活性受到Na_3VO_4和DES的强烈抑制,而不受Na_2MoO_4和NaN_3的抑制。溶解的酶液经透析后,K~ —ATP酶活性占Mg~(2 ),KCl—ATP酶活性的85％。     

多元醇及肌醇代谢改变在糖尿病大血管病变中的作用

血管壁中多元醇活性增强引起山梨醇和果糖在细胞内堆积,造成细胞渗透性肿胀和破坏。山梨醇浓度增加直接或间接扰乱细胞内游离肌醇的利用。肌醇的减少,使磷脂酰肌醇合成受限,胞膜上磷脂酰肌醇池更新出现障碍,同时膜上磷酸肌醇也减低,导致膜Na~+-K~+-ATP酶活性减低。在高血糖与醛糖还原酶的共同作用下,醛糖与醇糖均增多,促进细胞外基质的非解性糖化,加重动脉壁的硬化。     

NaCl胁迫下大麦根系液泡膜H+-ATP酶活性受ATP和焦磷酸含量的调节

选用两个耐盐性强弱不同的大麦(Hordeumvulgare L.)品种,研究了NaCl胁迫下其幼苗根中ATP和焦磷酸(PPi)含量的变化以及PPi对液泡膜H -ATP酶活性的影响.结果表明:在含NaCl 200mmol/L的1/2 Hoagland溶液中处理2 d,耐盐品种(滩引2号)根中液泡膜H -ATP酶活性增加,然后逐渐下降,而H -PPi酶活性在NaCl处理9 d中'直下降.盐敏感品种(科品7号)在NaCl胁迫下根中H -ATP酶和H -PPi酶活性都下降(图1).与对照相比较,NaCl胁迫下耐盐品种根中ATP含量2 d时增加,4 d后下降;盐敏感品种根中ATP积累受NaCl胁迫的抑制(图2).NaCl胁迫下,两品种的PPi含量皆略有增加(图3).PPi对液泡膜H -ATP酶活性有竞争性抑制作用(图4).结果表明:ATP积累是NaCl胁迫下液泡膜H -ATP酶活性增加的原因之一,NaCl胁迫下大麦品种根中ATP含量下降和PPi对液泡膜H -ATP酶的抑制使该酶活性下降.     

久效磷对美国红鱼鳃Na^＋／K^＋-ATP酶活性和超显微结构的影响

经不同试验浓度的久效磷(0．25、0．5、1．0和2．0mg·L^-1)处理美国红鱼4d后,分别对鱼鳃Na^+／K^+—ATP酶活性和氯细胞密度进行了测定和计数,并观察了鱼鳃组织显微结构和超微结构的变化。结果表明,低浓度久效磷(0．25mg·L^-1)处理可以诱导鱼鳃氯细胞大量增生,Na^+／K^+—ATP酶活性增强,随着试验浓度的增加,久效磷对鳃组织的损伤越来越重,Na^+／K^+—ATP酶活性逐渐降低;久效磷对鱼鳃显微结构的损伤表现为鳃小片上皮细胞水肿、脱离。鳃小片基部粘连。鳃小片上皮细胞角质化;超微结构变化主要为内质网、线粒体、微小管和核膜的水肿及部分溶解,这种损伤表现为由细胞膜到细胞核的动态过程。     

植物质膜H^＋—ATPase的研究进展

植物质膜H~+-ATPase具有控制细胞内环境pH,产生电化学势梯度,促进离子及分子运输,控制细胞伸长生长等生理功能。它含有大约100kD的催化亚基,8～10个跨膜的螺旋,使ATP水解与H~+运输相偶联。酶活性受植物激素、脂类和蛋白激酶等因子调节。此酶已被成功地分离、纯化、重组和分子克隆。     

低氧应激下甘肃鼢鼠与SD 大鼠心脏抗氧化酶和ATP 酶活性的比较

为探讨低氧应激下甘肃鼢鼠心脏对抗氧化损伤和电生理紊乱的可能机制,对甘肃鼢鼠和SD 大鼠在4. 5%氧浓度下分别进行2 h、4 h、6 h、8 h、10 h、16 h 低氧应激,比较常氧和各时程低氧下二者心脏超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽还原酶(GR)和Ca^{2 +} - ATP 酶、Ca^{2 +} - Mg^{2 +} - ATP 酶、Na ⁺ - K ⁺ - ATP酶活性,以丙二醛(MDA)含量作为机体氧化损伤指标。结果显示,常氧组甘肃鼢鼠GR 活性比SD 大鼠高,SOD、CAT、Ca^{2 +}-ATP 酶、Ca^{2 +} - Mg^{2 +} - ATP 酶和Na ⁺ - K ⁺ - ATP 酶活性及MDA 含量与SD 大鼠相比均无显著性差
异;低氧组甘肃鼢鼠SOD、CAT、GR、Ca^{2 +} - ATP 酶、Ca^{2 +} - Mg^{2 +} - ATP 酶和Na ⁺ - K ⁺ - ATP 酶活性迅速升高,显著高于SD 大鼠,MDA 含量则显著低于SD 大鼠。说明甘肃鼢鼠心脏通过提高抗氧化酶活性清除低氧诱导产生的多余自由基,并通过提高ATP 酶活性保证心电活动正常、心率稳定,应对低氧应激。     

玉米杂种优势与杂交后胚中ATP酶活性和RNA酶活性及蛋白质含量的关系

通过对若干个玉米杂交及其亲本自交授粉后1天、3天、7天、10天胚中ATP酶活性、RNA酶活性及蛋白质变化的比较来探讨杂种优势产生的生化机理。结果表明,30个组合的玉米授粉后一天,有90%组合杂交胚中ATP酶活性超过双亲或母本自交胚中ATP酶活性。授粉后3天杂交胚中ATP酶活性多数低于双亲自交胚中的ATP酶活性,看来这一表现与自交授粉后胚中合子细胞分裂较迟缓有关。以上四个时期授粉后,杂交胚中RNA酶活性介于双亲之间或低于双亲,这可能与杂交胚中核酸分解的速度较慢有关。杂交胚中蛋白质含量变化不同时期各组合间表现不同,杂交后胚胎发育初期胚中蛋白质的变化不一定是总的数量的增加,而是某些蛋白质或酶的变化。     

Cardiac sarcolemmal Na+-Ca2+ exchange and Na+-K+ ATPase activities and gene expression in alloxan-induced diabetes in rats

To determine the sequence of alterations in cardiac sarcolemmal (SL) Na⁺-Ca²⁺ exchange, Na⁺-K⁺ ATPase and Ca²⁺-transport activities during the development of diabetes, rats were made diabetic by an intravenous injection of 65 mg/kg alloxan. SL membranes were prepared from control and experimental hearts 1-12 weeks after induction of diabetes. A separate group of 4 week diabetic animals were injected with insulin (3 U/day) for an additional 4 weeks. Both Na⁺-K⁺ ATPase and Ca²⁺-stimulated ATPase activities were depressed as early as 10 days after alloxan administration; Mg²⁺ ATPase activity was not depressed throughout the experimental periods. Both Na⁺-Ca²⁺ exchange and ATP-dependent Ca²⁺-uptake activities were depressed in diabetic hearts 2 weeks after diabetes induction. These defects in SL Na⁺-K⁺ ATPase and Ca-transport activities were normalized upon treatment of diabetic animals with insulin. Northern blot analysis was employed to compare the relative mRNA abundances of _--subunit of Na⁺-K⁺ ATPase and Na⁺-Ca²⁺ exchanger in diabetic ventricular tissue vs. control samples. At 6 weeks after alloxan administration, a significant depression of the Na⁺-K⁺ ATPase _-- subunit mRNA was noted in diabetic heart. A significant increase in the Na⁺-Ca²⁺ exchanger mRNA abundance was observed at 3 weeks which returned to control by 5 weeks. The results from the alloxan-rat model of diabetes support the view that SL membrane abnormalities in Na⁺-K⁺ ATPase, Na⁺Ca²⁺ exchange and Ca²⁺-pump activities may lead to the occurrence of intracellular Ca²⁺ overload during the development of diabetic cardiomyopathy but these defects may not be the consequence of depressed expression of genes specific for those SL proteins.     

Diabetes-induced decrease in rat brain microsomal Ca2+-ATPase activity

The Ca(2+)-ATPase activity of rat brain microsomes was studied in streptozotocin (STZ)-induced diabetes. Male rats, 200-250 g, were rendered diabetic by injection of STZ (45 mg kg(-1) body weight) via the teil vein. Brain tissues were collected at 1, 4 and 10 weeks after diabetes was induced for determination of Ca(2+)-ATPase activity, lipid peroxidation and tissue calcium levels. Diabetic rats had significantly elevated blood glucose levels compared to controls. Blood glucose levels were 92.92 +/- 1.22 mg dl(-1) (mean +/- SEM) for the control group, 362.50 +/- 9.61 mg dl(-1) at 1 week and >500 mg dl(-1) at 4, 8 and 10 weeks for the diabetics. Enzyme activities were significantly decreased at 1, 4, 8 and 10 weeks of diabetes relative to the control group (p < 0.001). Ca(2+)-ATPase activity was 0.084 +/- 0.008 U l(-1), 0.029 +/- 0.005 U l(-1), 0.029 +/- 0.006 U l(-1), 0.033 +/- 0.003 U l(-1) and 0.058 +/- 0.006 U l(-1) (mean +/- SEM) at control, 1, 4, 8 and 10 week of diabetes respectively. The change in calcium levels in diabetic rat brain at 8 and 10 weeks of diabetes was significantly higher than that of the control group (p < 0.05). On the other hand lipid peroxidation measured as TBARS (thiobarbituric acid reactive substances) was significantly higher at 8 and 10 weeks of diabetes (p < 0.05). The increase in lipid peroxidation observed in diabetic rat brain may be partly responsible for the decrease in calcium ATPase activity.     

Differential changes in cardiac myofibrillar and sarcoplasmic reticular gene expression in alloxan-induced diabetes

In order to examine the relationship between heart dysfunction and subcellular abnormalities as well as molecular mechanisms during the development of diabetes, we studied changes in cardiac performance, myofibrillar as well as sarcoplasmic reticular (SR) activities, and cardiac gene expression at different time intervals upon inducing diabetes in rats by an injection of alloxan (65 mg/kg; i.v.). Cardiac dysfunction was associated with a depression in myofibrillar Ca²⁺-stimulated ATPase and changes in myosin isozyme composition at 2-12 weeks of inducing diabetes. A reduction in SR Ca²⁺-uptake and Ca²⁺-pump (SERCA2) activities was evident at 10 days to 12 weeks of inducing diabetes. Alterations in cardiac function during 2-12 weeks of diabetes show a linear relationship with changes in myofibrils and SR membranes. Furthermore, alterations in cardiac function as well as myofibrillar and SR activities in 4 week diabetic animals were normalized upon treatment with insulin for 4 weeks. The steady-state mRNA abundance for -myosin heavy chain in the heart was decreased at 2 and 3 weeks but was unchanged at 5 and 6 weeks, whereas mRNA levels for -myosin heavy chain remained elevated during 2-6 weeks after inducing diabetes. SERCA2 mRNA abundance in diabetic heart was significantly increased at 3 and 5 weeks but was unaltered at 2 and 6 weeks. These results support the view that heart dysfunction in diabetes may be a consequence of myofibrillar and SR abnormalities; however, defects in myofibrillar proteins, unlike those in the SR membranes, appear to be due to changes in their gene expression.     

Ganglioside treatment of diabetic rats; effects on nerve adenosine triphosphatase activity and motor nerve conduction velocity

Ouabain-sensitive ATPase activity (expressed as nmol ADP produced/h/mg (wet) nerve +/- SEM) was measured in homogenates of sciatic nerve from control rats and rats with streptozotocin-induced diabetes of 8 wk duration. Nerves from diabetic rats showed activity (21.7 +/- 2.0) which was significantly (p less than 0.05) less than that of controls (34.6 +/- 4.8). These animals also showed a deficit in conduction velocity (m/sec +/- SEM) of sciatic nerve motoneurones (50.7 +/- 0.4 vs. 57.7 +/- 0.7 in controls; p less than 0.001). In parallel, matched control and diabetic groups were treated daily with mixed gangliosides extracted from bovine brain (10 mg/kg i.p.). After such treatment for 8 wk the deficit in ouabain-sensitive ATPase activity did not develop in the diabetic group (treated diabetics, 31.9 +/- 3.7; treated controls, 34.5 +/- 3.8). However, the treatment did not affect the deficit in motor nerve conduction velocity (treated diabetics, 50.9 +/- 1.1 vs. treated controls, 57.9 +/- 0.5; p less than 0.001). Accumulations of the polyol pathway metabolites--sorbitol and fructose--together with depletion of nerve myo-inositol were similar in both diabetic groups. These data indicate an etiology for the conduction velocity deficit which differs from that of the deficit in ouabain-sensitive ATPase.     

Modification of myosin isozymes and SR Ca2+-pump ATPase of the diabetic rat heart by lipid-lowering interventions

To define metabolic influences on cardiac myosin expression and sarcoplasmic reticulum (SR) Ca²⁺-stimulated ATPase streptozotocin-diabetic rats were treated for 9–10 wk with etomoxir, an inhibitor of carnitine palmitoyl transferase I (CPT-1) and fatty acid synthesis, or an antilipolytic drug, acipimox. Etomoxir reduced myosin V₃ of diabetic rats but did not normalize it. However, the high serum triglyceride, free-fatty acid and cholesterol concentrations in diabetic animals were greatly reduced. After bypassing the CPT-1 inhibition with a medium-chain fatty acid (miglyol) diet, the V₃ contents and serum lipids were still reduced in the etomoxir-treated diabetic rats; V₃ was also reduced in diabetic rats fed miglyol or treated with acipimox. Since low serum insulin or triiodothyronine concentrations in diabetic rats were not improved by these interventions but changes in V₃ were correlated with those in triglyceride, free-fatty acid and cholesterol concentrations, it is likely that myosin may be influenced by some metabolic factors. To assess the role of adrenergic influences, diabetic rats (7–8 wk) were treated with an antisympathotonic drug, moxonidine, a -adrenoceptor blocking drug, propranolol, and a bradycardic drug, tedisamil. Myosin V₃ was not reduced significantly in moxonidine-treated or propranolol-treated rats in comparison to untreated diabetic rats. Serum thyroid hormones and insulin were not altered, whereas triglycerides were reduced but not significantly by these antiadrenergic agents. Lowering serum lipids in diabetic rats by treatment with etomoxir, miglyol and acipimox increased the depressed SR Ca²⁺-stimulated ATPase activity. On the other hand, in diabetic rats treated with moxonidine, propranolol or tedisamil, the ATPase activity was not increased significantly. These results suggest that normalization of blood lipids is important for improving subcellular organelle function in diabetic hearts with impaired glucose utilization.     

Chronic taurine supplementation ameliorates oxidative stress and Na+ K+ ATPase impairment in the retina of diabetic rats

Summary.  This study evaluates the effect of 4 months supplementation with 2% and 5% taurine (w/w) on the retina of diabetic rats. In non-diabetic rats, taurine does not modify glycemia, body weight, retinal conjugated dienes (CD), lipid hydroperoxide (LP), and Na⁺K⁺ATPase activity. In diabetic rat, at 2, 4, 8, 16 weeks following the onset of diabetes, retinal CD and LP are significantly and progressively increased, while pump activity is gradually and significantly reduced. In taurine supplemented diabetic rats, glycemia is not affected but lipid peroxidation is significantly decreased. Finally, taurine preserves ATPase activity being 5% more effective than 2% taurine. We conclude that taurine supplementation ameliorates biochemical retinal abnormalities caused by diabetes, thereby suggesting that taurine may have a role in the prevention of retinal changes in diabetes. Received November 26, 2001 Accepted January 10, 2002 Published online October 3, 2002 Authors' address: Prof. Flavia Franconi, Department of Pharmacology, University of Sassari, Via Muroni 23a, I-07100 Sassari, Italy, Fax: 39-79228715, E-mail: franconi@ssmain.uniss.it     

Antioxidative and anti-diabetic effects of amaranth (Amaranthus esculantus) in streptozotocin-induced diabetic rats

The anti-diabetic and antioxidative effect of amaranth grain (AG) and its oil fraction (AO) was studied in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into four groups after induction of STZ-diabetes: normal control; diabetic control; diabetic-AG supplement (500 g kg(-1) diet); diabetic-AO supplement (100 g kg(-1) diet) and fed experimental diets for 3 weeks. Serum glucose, insulin, activities of serum marker enzymes of liver function and liver cytosolic antioxidant enzymes were measured. The AG and AO supplement significantly decreased the serum glucose and increased serum insulin level in diabetic rats. Serum concentration of liver function marker enzymes, GOT and GPT, were also normalized by AG and AO treatment in diabetic rats. Liver cytosolic SOD and GSH-reductase activities were significantly increased, and catalase, peroxidase and GSH-Px activities were decreased in diabetic rats. AG and AO supplement reverted the antioxidant enzyme activities to near normal values. Hepatic lipid peroxide product was significantly higher, and GSH content was decreased in diabetic rats. However, AG and AO supplement normalized these values. Our data suggest that AG and AO supplement, as an antioxidant therapy, may be beneficial for correcting hyperglycaemia and preventing diabetic complications.     

Inhibitory action of opioid peptides on ouabain-sensitive Na+-K+ and Ca2+-dependent ATPase activities in bovine cardiac sarcolemma

The present study demonstrates that morphine (10(-6) and 10(-5) M), methionine-enkephalin or leucine-enkephalin (10(-10), 10(-8), and 10(-6) M) were able to inhibit significantly, in a dose-dependent manner, both the sarcolemmal Ca2+-dependent ATPase and the ouabain-sensitive Na+-K+ ATPase activities. The inhibitory action of these opioids on the two ATPases was not antagonized by preincubation with naloxone (10(-6) M). Naloxone alone (10(-8), 10(-6) and 10(-5) M) did not affect both the sarcolemmal Ca2+-dependent ATPase and the ouabain-sensitive Na+-K+ ATPase activities. Heat-denatured methionine-enkephalin (10(-6) M) or leucine-enkephalin (10(-6) M) also unaffected both the ATPases. The possibility is also discussed that opioid peptides may regulate myocardial contractility by modulating the movement of ions across the heart sarcolemma.     

Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats

In the current study, the effect of soy protein and genistein, one of the main isoflavones in soybeans, on blood glucose, lipid profile, and antioxidant enzyme activities in streptozotocin (STZ)-induced diabetic rats was investigated. Male Sprague-Dawley rats were divided into nondiabetic control, STZ, STZ-genistein supplemented group (STZ-G; 600 mg/kg diet), and STZ-isolated soy protein supplemented group (STZ-ISP; 200 g/kg diet). Diabetes was induced by a single injection of STZ (50 mg/kg BW) freshly dissolved in 0.1 mol/L citrate buffer (pH 4.5) into the intraperitonium. Diabetes was confirmed by measuring the fasting blood glucose concentration 48-h post-injection. The rats with blood glucose level above 350 mg/dL were considered to be diabetic. Genistein and ISP were supplemented in the diet for 3 weeks. The supplementation of genistein and ISP increased the plasma insulin level but decreased the HbA(IC) level of the STZ-induced diabetic rats. The supplementation of genistein and ISP increased the glucokinase level of the STZ-induced diabetic rats. A significant reduction in glucose-6-phosphatase was observed in the groups treated with genistein and ISP in comparison with the diabetic control group. Hepatic superoxide dismutase, catalase, and glutathione peroxidase activities of the STZ-induced diabetic rats were significantly decreased in comparison with the control rats. Administering genistein and ISP to the STZ-induced diabetic rats significantly increased those enzyme activities. The concentration of thiobarbituric acid reactive substances in the STZ-induced diabetic rats was significantly elevated, while the genistein and ISP supplement decreased it to the control concentration. Genistein and ISP supplements seem to be beneficial for correcting the hyperglycemia and preventing diabetic complications.