Cardamonin stimulates glucose uptake through translocation of glucose transporter-4 in L6 myotubes

Glucose transporter-4 (GLUT4) is a transmembrane protein that plays a major role in insulin-mediated glucose transport in muscle and adipocytes. For glucose transport to occur, the GLUT4 protein needs to be translocated from the intracellular pool to the plasma membrane, and certain compounds may enhance this process. The present study investigated the promotion of glucose uptake in differentiated L6 myotubes by cardamonin, isolated from Alpinia katsumadai. Cardamonin increased translocation of GLUT4 to the plasma membrane in L6 cells, but did not activate protein kinase C ζ/λ, Akt, or AMP-activated protein-kinase, all of which are known to regulate GLUT4 translocation. The glucose-uptake-promoting activity of cardamonin was not lowered by treatment with a phosphatidylinositol 3'-kinase inhibitor. These results suggest that cardamonin is a promising active compound for maintaining glucose homeostasis, and that it acts via an unknown mechanism that does not involve activation of the downstream insulin signal and AMP-activated protein kinase.     

Polyphenols-rich Vernonia amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats

Aim of the study

This study aims to investigate the hypoglycemic properties of Vernonia amygdalina Del. (VA) and its possible mechanisms of action in a single-dose STZ induced diabetic rat model.

Materials and methods

A dose-response study was conducted to determine optimum dose for the hypoglycemic effect of VA in STZ-induced diabetic rats. The optimum dose (400 mg/kg) was used throughout the 28-day chronic study. Body weight, food and water intakes of the rats were monitored daily. Fasting blood serum, pancreas, liver and soleus muscle were collected for biochemical analyses. Chemical composition of VA was analysed using HPLC and LC-ESI-MS.

Results

The study reveals that ethanolic extract of VA contains high level of polyphenols mainly 1,5-dicaffeoyl-quinic acid, dicaffeoyl-quinic acid, chlorogenic acid and luteolin-7-O-glucoside. In an oral glucose tolerance test, 400 mg/kg VA exhibited a significant improvement in glucose tolerance of the STZ-induced diabetic rats. 28-day treatment with 400 mg/kg VA resulted in 32.1% decrease in fasting blood glucose compared to diabetic control. VA also caused significant decrease (18.2% and 41%) in triglyceride and total cholesterol level. Besides, VA showed protective effect over pancreatic β-cells against STZ-induced damage, causing a slight increase in insulin level compared to diabetic control. VA administration also showed positive regulation of the antioxidant system, both enzymatic and non-enzymatic. Furthermore, VA was found to increase expression of GLUT 4 (24%) in rat skeletal muscle. Further tissue fractionation revealed that it can increase the GLUT 4 translocation (35.7%) to plasma membrane as well, suggesting that VA may stimulate skeletal muscle's glucose uptake. This observation is in line with the restoration in skeletal muscle glycogenesis of VA-treated group. However, no alteration was observed in GLUT 1 expression. In addition, VA also suppressed (40% inhibition) one of the key hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase).

Conclusions

VA possesses antihyperglycemic effect, most probably through increasing GLUT 4 translocation and inhibiting hepatic G6Pase. The polyphenols in the extract may be the candidates that are responsible for the above-mentioned biological activities.     

SDF7, a group of Scoparia dulcis Linn. derived flavonoid compounds,stimulates glucose uptake and regulates adipocytokines in 3T3-F442a adipocytes

Ethnopharmacology relevance

Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes.

Material and methods

Morphology and lipid accumulation of differentiated 3T3-F442a adipocytes by 100 nM insulin treated with different concentrations of SDF7 and rosiglitazone were examined followed by the evaluation of glucose uptake activity expressions of insulin signalling downstream components (IRS-1, PI3-kinase, PKB, PKC, TC10 and GLUT4) from four cellular fractions (plasma membrane, cytosol, high density microsome and low density microsome). Next, the expression level of adipocytokines (TNF-α, adiponectin and leptin) and immunoblotting of treated 3T3-F442 adipocytes was determined at 30 min and 480 min. Glucose transporter 4 (GLUT4) translocation of 3T3-F442a adipocytes membrane was also determined. Lastly, mRNA expression of adiponectin and PPAR-γ of 3T3-F442a adipocytes were induced and compared with basal concentration.

Results

It was found that SDF7 was able to induce adipocytes differentiation with great extends of morphological changes, lipid synthesis and lipid stimulation in vitro. SDF7 stimulation of glucose transport on 3T3-F442a adipocytes are found to be dose independent, time-dependent and plasma membrane GLUT4 expression-dependent. Moreover, SDF7 are observed to be able to suppress TNF-α and leptin expressions that were mediated by 3T3-F442a adipocytes, while stimulated adiponectin secretion on the cells. There was a significant expression (p<0.01) of protein kinase C and small G protein TC10 on 3T3-F442a adipocytes upon treatment with SDF7 as compared to the control. SDF7 was also found to be effective in stimulating adiponectin and PPAR-γ mRNA upregulation at 50 µg/ml.

Conclusion

SDF7 exhibited good lipogenesis, adiponectinesis and glucose uptake stimulatory properties on 3T3-F442a adipocytes.     

Tinospora cordifolia preserves pancreatic beta cells and enhances glucose uptake in adipocytes to regulate glucose metabolism in diabetic rats

The purpose of this study was to evaluate the pancreatic beta cell protective and glucose uptake enhancing effect of the water extract of Tinospora cordifolia stem (TCSE) by using rat insulinoma (RIN)‐m5F cells and 3 T3‐L1 adipocytes. RIN‐m5F cells were stimulated with interleukin‐1β and interferon‐γ, and the effect of TCSE on insulin secretion and cytokine‐induced toxicity was measured by ELISA and MTT assay, respectively. The glucose uptake and protein expression were measured by fluorometry and western blotting. Antidiabetic effect of TCSE was measured using streptozotocin‐induced diabetic rats. TCSE dose dependently increased cell viability and insulin secretion in RIN‐m5F cells. In addition, TCSE increased both the glucose uptake and glucose transporter 4 translocation in 3 T3‐L1 adipocytes via PI3K pathway. Finally, TCSE significantly lowered blood glucose and diet intake and increased body weight in streptozotocin‐induced diabetic rats. The level of serum insulin and hepatic glycogen was increased, whereas the level of serum triglyceride, total cholesterol, dipeptidyl peptidase‐4, and thiobarbituric acid reactive substances was decreased in TCSE‐administered rats. TCSE also increased glucose transporter 4 protein expression in the adipose tissue and liver of TCSE‐fed diabetic rats. Our results suggested that TCSE preserved RIN‐m5F cells from cytokine‐induced toxicity and enhanced glucose uptake in 3 T3‐L1 adipocytes, which may regulate glucose metabolism in diabetic rats.     

Antihyperglycemic and insulin secretory activity of Costus pictus leaf extract in streptozotocin induced diabetic rats and in in vitro pancreatic islet culture

Aim of the study

The leaves of Costus pictus D. Don were used extensively for its antihyperglycemic activity by the people in Kerala, India. In the present study, the antihyperglycemic and insulin secretory activity of an aqueous extract of Costus pictus leaf extract was investigated in streptozotocin induced diabetic rats.

Materials and methods

Oral Glucose Tolerance Test was done to determine the effective dose of Costus pictus extract. Aqueous extract of Costus pictus leaves was given orally to the diabetic rats for 14 days. The insulin secretory action of the leaf extract was investigated using isolated pancreatic islets from rat. Liver glucose uptake activity was measured using d-[¹⁴C] glucose.

Results

The oral administration of an aqueous extract of Costus pictus at a dose of 250 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in diabetic rats at the end of 14 days treatment. The Costus pictus leaf extract significantly increased glucose induced insulin secretion at both 4 mM and 20 mM glucose concentrations which represents normal physiological and diabetic condition respectively. The decreased glucose uptake activity of the liver of diabetic rats was reverted to near normal levels after the treatment with Costus pictus leaf extract.

Conclusion

Our results suggest the glucose lowering effect of Costus pictus to be associated with the potentiation of insulin release from pancreatic islets and enhancement of peripheral utilization of glucose.     

桑叶提取物调控IRS-1/PI3K/GLUT4通路影响2型糖尿病胰岛素抵抗机制研究

目的:提取桑叶中的黄酮类及多酚类物质,观察其对2型糖尿病(T2DM)模型大鼠降血糖及改善胰岛素抵抗(IR的作用,并探讨其分子机制。方法:取雄性SD大鼠,分为正常组、模型组、二甲双胍组、桑叶提取物组,除正常组以外建立T2DM模型,灌胃干预4周,观察药物对模型大鼠一般情况、生化指标、骨骼肌病理等的影响。测定胰岛素受体底物-1 (IRS-1)、磷脂酰肌醇3-激酶(PI3K)中的p85α、葡萄糖转运体-4 (GLUT4)在骨骼肌组织中的信使核糖核酸(mRNA)及蛋白表达水平。结果:与正常组比较,模型组空腹血糖(FBG)、IR稳态模型指数(HOMA-IR)、血清胰岛素、总胆固醇、甘油三酯、低密度脂蛋白水平升高(P<0.05);IRS-1、PI3K p85α、GLUT4的mRNA及蛋白表达明显下降(P<0.05)。与模型组比较,桑叶提取物组FBG、HOMA-IR、总胆固醇、甘油三酯、低密度脂蛋白水平下降(P<0.05);IRS-1、PI3K p85α、GLUT4的mRNA及蛋白表达明显升高(P<0.05);二甲双胍组FBG有所下降,但差异无统计学意义,血清胰岛素及HOMA-...     

Ibervillea sonorae (Cucurbitaceae) induces the glucose uptake in human adipocytes by activating a PI3K-independent pathway

Ethnopharmacological relevance

Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE).

Materials and methods

Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques.

Results

ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid.

Conclusion

Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independant pathway and without proadipogenic effects.     

基于GLUT4转位的中药及活性成分改善胰岛素抵抗研究进展

对中药通过调控葡萄糖转运蛋白4(glucose transporter 4,GLUT4)转位而改善胰岛素抵抗(insulin resistance,IR)的研究进展进行总结.GLUT4转位研究对IR的机制研究以及药物作用靶点的选择都具有重要意义.本文主要从磷脂酰肌醇3-激酶/非典型蛋白激酶C/蛋白激酶B(PI3K/ PKC/ Akt),AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)等关键途径,介绍各种中药活性成分、单方及复方通过调控GLUT4转位对IR的改善作用及机制,为防治IR中药的临床合理使用及新药开发提供参考.     

Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats

The antihyperglycemic action of puerarin, purified from the roots of Pueraria lobata, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Bolus intravenous injection of puerarin decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Similar treatment with puerarin also decreased the plasma glucose in normal rats, although the effect was not as great as that in STZ-diabetic rats. Puerarin at the effective dose (15.0 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. In the isolated soleus muscle of STZ-diabetic rats, puerarin enhanced the uptake of radioactive glucose in a concentration-dependent manner. Moreover, the mRNA and protein levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle were increased after repeated intravenous administration of puerarin in STZ-diabetic rats for 3 days. These results suggest that puerarin can increase the glucose utilization to lower plasma glucose in diabetic rats lacking insulin.     

Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats

This study investigated the effect of aqueous and ethanol soluble solid extracts of guava (Psidium guajava Linn.) leaves on hypoglycemia and glucose metabolism in type 2 diabetic rats. Low-dose streptozotocin (STZ) and nicotinamide were injected into Sprague-Dawley (SD) rats to induce type 2 diabetes. Acute and long-term feeding tests were carried out, and an oral glucose tolerance test (OGTT) to follow the changes in plasma glucose and insulin levels was performed to evaluate the antihyperglycemic effect of guava leaf extracts in diabetic rats.The results of acute and long-term feeding tests showed a significant reduction in the blood sugar level in diabetic rats fed with either the aqueous or ethanol extract of guava leaves (p < 0.05). Long-term administration of guava leaf extracts increased the plasma insulin level and glucose utilization in diabetic rats. The results also indicated that the activities of hepatic hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed with aqueous extracts were higher than in the normal diabetic group (p < 0.05). On the other hand, diabetic rats treated with the ethanol extract raised the activities of hepatic hexokinase and glucose-6-phosphate dehydrogenase (p < 0.05) only. The experiments provided evidence to support the antihyperglycemic effect of guava leaf extract and the health function of guava leaves against type 2 diabetes.     

Dangnyohwan improves glucose utilization and reduces insulin resistance by increasing the adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokushima Fatty rats

AIM OF THE STUDY: Dangnyohwan (DNH) has been used for treatment of diabetes mellitus. However, the exact cellular and molecular mechanisms underlying the beneficial effects of DNH are not well understood. Therefore, we investigated how DNH improves hyperglycemia and insulin resistance in obese-type diabetes model. METHODS AND MATERIALS: We examined the effect of DNH on the expression of glucose transporter 4 (GLUT4), GLUT4 translocation, and glucose transport activity in muscle and adipose tissues from Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats. RESULTS: DNH ameliorated hyperglycemia and impaired glucose tolerance (IGT) observed in 26- and 42-week-old male OLETF rats. The basal and insulin-stimulated [14C]2-Deoxyglucose (2DG) uptake was significantly increased in adipocytes from DNH-treated OLETF rats, as compared with untreated OLETF rats. The expression level of GLUT4 was markedly decreased (by 90-95%) in the adipose tissue of OLETF rats, whereas DNH treatment drastically increased the expression of GLUT4 within 8 weeks. DNH improved GLUT4 recruitment stimulated by insulin in both the 26- and 42-week-old OLETF rat adipocytes. CONCLUSION: These results suggest that DNH could exert the beneficial effects on hyperglycemia and insulin resistance by increasing the expression and insulin-stimulated translocation of GLUT4 in OLETF rat adipocytes.     

Ginsenoside Re reduces insulin resistance through activation of PPAR-γ pathway and inhibition of TNF-α production

Ethnopharmacological relevance

Panax ginseng is a well-known traditional Chinese medicine and has been used for treatment of various diseases for more than four thousand years in Asia. Ginseng saponins or ginsenosides, the active constituents are reported to possess antidiabetic activity, but their antihyperglycemic mechanisms are not fully elucidated. In the present study, the mechanisms of action of ginsenoside Re were investigated in vitro models.

Materials and methods

3T3-L1 cells were chosen as the model to investigate the molecular mechanisms of action of ginsenoside Re. Influence of ginsenoside Re on the adipogenesis was examined by determining TG levels in 3T3-L1 adipocytes by the method of TG oxidation enzyme. Glucose uptake in 3T3-L1 cells stimulated by insulin in the absence or presence of ginsenoside Re were quantified by measuring ³H-2-deoxy-d-glucose levels. Cytokine proteins released into the medium including adiponectin and TNF-α were tested using respective ELISA kits. In addition, real time RT-PCR was conducted to investigate the expression changes of PPAR-γ and its responsive genes, ap2, adiponectin, IRS-1, GLUT4 and TNF-α. And western blot analysis was performed to determine the translocation of GLUT4. Finally, effects of ginsenoside Re on NO production in 3T3-L1 adipocytes and in macrophages were investigated through measurement of nitrite concentration by Griess reagent.

Results

Ginsenoside Re induced adipogenesis of 3T3-L1 adipocytes by accumulating TG, increased glucose uptake and up-regulated PPAR-γ2, IRS-1, ap2 and adiponectin genes expressions. Meanwhile, Re also increased production and release of adiponectin. Although having no effects on GLUT4 gene expression, Re facilitated GLUT4 protein translocation to the membranes. In addition, Re inhibited the expression and release of TNF-α. Finally, Re did not show inhibitory effects on NO production both in 3T3-L1 cells stimulated by LPS, TNF-α and IFN-γ and in LPS-stimulated mouse peritoneal macrophages.

Conclusions

Ginsenoside Re exhibited the action of reducing insulin resistance through activation of PPAR-γ pathway by directly increasing the expressions of PPAR-γ2 and its responsive genes, adiponectin, IRS-1, ap2, inhibiting TNF-α production and facilitating the translocation of GLUT4 to promote glucose uptake and disposal in 3T3-L1 adipocytes.     

Inhibitory effect of pomegranate on intestinal sodium dependent glucose uptake

Intestinal glucose uptake is mainly performed by its specific transporters, SGLT1 and GLUTs expressed in the intestinal epithelial cells. By using Caco-2 cells and 2-NBDG, we observed that intestinal glucose uptake was markedly inhibited by pomegranate (Punica granatum L, PG) among 200 screened edible Korean plants. The effects of the PG extract on Na(+)-dependent glucose uptake were further evaluated using brush border membrane vesicles (BBMV) obtained from the mouse small intestine. PG inhibited Na(+)-dependent glucose uptake with the IC(50) value of 424 μg/ml. The SGLT1 protein expression was dose dependently down regulated with PG treatment in Caco-2 cells. We next assessed the antihyperglycemic effect of PG in streptozotocin (STZ)-induced diabetic mice. Administration of PG (800 mg/kg) to STZ mice for four weeks improved postprandial glucose regulation. Furthermore, elevated Na(+)-dependent glucose uptake by BBMV isolated from STZ mice was normalized by PG treratment. These results suggest that PG could play a role in controlling the dietary glucose absorption at the intestinal tract by decreasing SGLT1 expression, and may contribute to blood glucose homeostasis in the diabetic condition.     

Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in High‐Fat Diet/Streptozotocin‐Induced Type 2 Diabetic Rats

Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high‐fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non‐esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator‐activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα‐protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.     

Increasing brain glucose uptake by Gypenoside LXXV ameliorates cognitive deficits in a mouse model of diabetic Alzheimer's disease

We have previously reported that Gypenoside LXXV (GP-75), a novel natural PPARγ agonist isolated from Gynostemma pentaphyllum, ameliorated cognitive deficits in db/db mice. In this study, we further investigated the beneficial effects on cognitive impairment in APP/PS1 mice and a mouse model of diabetic AD (APP/PS1xdb/db mice). Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 3 months significantly attenuated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice. GP-75 treatment markedly reduced the levels of glucose, HbA1c and insulin in serum and improved glucose tolerance and insulin sensitivity in APP/PS1xdb/db mice. Notably, GP-75 treatment decreased the β-amyloid (Aβ) burden, as measured by ¹¹C-PIB PET imaging. Importantly, GP-75 treatment increased brain glucose uptake as measured by ¹⁸F-FDG PET imaging. Moreover, GP-75 treatment upregulated PPARγ and increased phosphorylation of Akt (Ser473) and GLUT4 expression levels but decreased phosphorylation of IRS-1 (Ser616) in the hippocampi of both APP/PS1 and APP/PS1xdb/db mice. Furthermore, GP-75-induced increases in GLUT4 membrane translocation in primary hippocampal neurons from APP/PS1xdb/db mice was abolished by cotreatment with the selective PPARγ antagonist GW9662 or the PI3K inhibitor LY294002. In summary, GP-75 ameliorated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice by enhancing glucose uptake via activation of the PPARγ/Akt/GLUT4 signaling pathways.     

Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic rats

The antihyperglycemic effect of syringaldehyde (1), purified from the stems of Hibiscus taiwanensis, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats) showing type-1 like diabetes mellitus. Bolus intravenous injection of 1 showed antihyperglycemic activity in a dose-dependent manner in STZ-diabetic rats. An effective dose of 7.2 mg/kg of 1 attenuated significantly the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. A glucose uptake test showed that 1 exhibits an increase of glucose uptake activity in a concentration-related manner. Moreover, an effect by 1 was shown for insulin sensitivity in STZ-diabetic rats. The compound was found to increase insulin sensitivity in STZ-diabetic rats. These results suggest that syringaldehyde (1) can increase glucose utilization and insulin sensitivity to lower plasma glucose in diabetic rats.     

银杏叶提取物增强糖尿病大鼠模型膈肌摄取葡萄糖能力的作用研究

目的:观察银杏叶提取物(GbE)对糖尿病大鼠模型膈肌葡萄糖摄取率和葡萄糖转运体4(GLUT4)mRNA表达水平的影响.方法:40只雄性SD大鼠随机分为正常对照组10只,造模组30只.应用高糖高脂饮食加小剂量链脲佐菌素诱发糖尿病大鼠模型.随机选取造模成功大鼠20只均分成2组:糖尿病组、GbE治疗组.GbE治疗组按8 mg·kg~(-1)·d~(-1)剂量腹腔注射GbE,持续8周.检测各组大鼠空腹血糖和胰岛素水平,膈肌组织葡萄糖摄取率和CLUT4 mRNA水平,并观察其超微结构的变化.结果:与正常对照组比较,糖尿病组大鼠空腹血糖和胰岛素升高(P<0.01);膈肌葡萄糖摄取率和GLUT4 mR-NA水平下降(P<0.05,P<0.01);电镜下主要表现为膈肌线粒体扩张,嵴变短,空泡化.GbE治疗组L述变化明显减轻.结论:GbE可部分纠正糖尿病大鼠模型高血糖、高胰岛素状态,并减轻膈肌损伤,其作用与增强膈肌GLUT4基因表达,促进膈肌对葡萄糖的摄取和利用有关.     

桑椹乙酸乙酯萃取物对链脲佐菌素致高血糖大鼠的降血糖作用

目的 研究桑椹乙酸乙酯萃取物(EEM)对链脲佐菌素(STZ)诱导的糖尿病大鼠的降糖作用.方法 用STZ诱导出1型糖尿病大鼠模型分成5组,分别用水、格列苯脲和0.1、0.2、0.3g/kg EEM连续灌胃3周,每周测定血糖.结果 与模型对照组相比,0.2 g/kg EEM能显著降低糖尿病大鼠血糖、糖化血清蛋白,刺激胰岛素分泌,增加体质量,调节血脂,增强机体抗氧化能力,同时具有一定的保护肾脏的功能,但对肝脏有一定副作用.结论 EEM能有效的控制糖尿病大鼠血糖水平,一定程度改善糖脂代谢紊乱.     

Mechanistic studies on the antidiabetic activity of a polysaccharide-rich extract of Radix Ophiopogonis

To study the hypoglycemic mechanisms of a polysaccharide-rich extract of Radix Ophiopogonis, the influences of the extract on activity of NIT-1 insulinoma cells damaged by streptozotocin (STZ), activity of α-glucosidase, glucose absorption into intestinal brush border membrane vesicles, gluconeogenesis by H4IIE hepatoma cells and glucose uptake by 3T3-L1 adipocytes were investigated. The results show that the extract improved the activity of NIT-1 cells damaged by STZ, inhibited glucose absorption into intestinal brush border membrane vesicles and reduced the activity of α-glucosidase. However, gluconeogenesis in H4IIE cells and glucose uptake in 3T3-L1 adipocytes did not change significantly in the presence of the extract. These results suggest that the hypoglycemic mechanisms of the polysaccharide-rich extract of Radix Ophiopogonis are caused by protection in pancreatic islet cells and the inhibition of carbohydrate digestion and absorption. This is possibly the first report on the underlying mechanisms responsible for the antidiabetic effect of Radix Ophiopogonis.