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1.
The antidiabetic activity of various subfractions of the alcohol extract of the bark of Pterocarpus marsupium Roxb. was evaluated in alloxan-induced diabetic rats. The effect of these extracts on lipid profile and liver function tests were also assessed to evaluate their activity in controlling diabetes related metabolic alterations. The parameters measured were plasma glucose, total protein, cholesterol, triglycerides, alkaline phosphatase, SGOT and SGPT. The results indicate the effective role of Pterocarpus marsupium on the above mentioned parameters indicating that Pterocarpus marsupium can also control the diabetes related metabolic alterations apart from controlling the glucose levels. Among the fractions tested the butanol subfraction was found to be more active in comparison with other subfractions. It can be concluded that the butanol subfraction of the alcohol extract of Pterocarpus marsupium exhibits significant antidiabetic activity and corrects the metabolic alterations in diabetic rats and this activity may resemble insulin-like properties.  相似文献   

2.

Ethnopharmacological relevance

Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor.

Aims of study

The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARγ) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent.

Materials and methods

Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-d-[1-3H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPARγ and PI3K have been studied.

Results

The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 μg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPARγ and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake.

Conclusion

This study demonstrated the significance of Glut-4, PPARγ and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.  相似文献   

3.
4.
Mulberry (Morus alba L.) leaf tea is promoted for its health benefits and the control of diabetes in Asian nations. The blood glucose lowering activity of mulberry leaf extract (MA) has been proven; however, the molecular basis underlying this effect remains unclear. The aim of the present work is to elucidate its mechanism of the antihyperglycemic action, by examining the effect of MA on glucose uptake and the translocation of glucose transporter 4 protein (GLUT4) to the plasma membrane of adipocytes isolated from diabetic rats. The incubation of adipocytes with 5-45 μg/ml MA resulted in 31-54% increase of glucose uptake in a dose-dependent manner. This glucose uptake enhancing effect was inhibited by the phosphoinositol 3-kinase (PI3-K) inhibitor, wortmannin (100 nM). The GLUT4 protein on the plasma membrane fraction of adipocytes was markedly increased after treatment with 15 μg/ml MA extract. Interestingly, gallic acid, one of the phenolic compounds found in MA extract, increased glucose uptake and enhanced the translocation of GLUT4 at concentrations comparable to the amount of gallic acid in the effective concentration ranges of MA. Thus, it is likely that gallic acid contributes, at least in part, to its antihyperglycemic activity. The present results suggest that the antihyperglycemic action of MA is mediated by increasing glucose uptake via the activation of PI3-K signaling pathway and translocation of GLUT4 to the plasma membrane. These findings are the first molecular evidence supporting the mulberry tea as herbal medicine for diabetic patients.  相似文献   

5.
Ginsenosides, the active component of Panax ginseng, have been shown to evidence a variety of biological activities associated with hyperglycemia, obesity and type 2 diabetes mellitus. This study evaluated the effects of the ginsenosides, Rg3 and Re, on glucose uptake and the glucose transport system in mature 3T3‐L1 cells. The results demonstrated that the glucose uptake of ginsenosides Rg3 and Re at concentrations of 1–10 µM significantly increased by approximately ~10% and ~12%, respectively. Furthermore, the glucose transporter 4 (GLUT4) mRNA expression of ginsenosides Rg3 and Re at 10 µM was increased by approximately ~1.73 and 1.43 fold, respectively. It was further confirmed in a series of experiments that ginsenosides Rg3 and Re stimulated the mRNA expression of insulin receptor substrate (IRS‐1) and the expression of phosphatidylinositol 3‐kinase (PI3K)‐110α protein, which is involved in downstream events in the insulin signaling pathway. These findings demonstrate that ginsenosides Rg3 and Re may stimulate glucose uptake via the PI3K pathways involving IRS‐1. Further, our results suggest that both of these ginsenosides might prove useful as effective antidiabetic and antihyperglycemic agents. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

6.
目的:探讨针刺改善痴呆、提高学习记忆能力的机制。方法:采用多发性梗塞痴呆(MID)大鼠为模型,运用Morris水迷宫评价动物的认知能力;Western blot法测定MID大鼠海马组织葡萄糖转运蛋白(Glut)1和3的表达。结果:MID大鼠学习能力和记忆保持能力明显损伤,需要花费更多时间找到水中平台。海马Glut1和Glut3表达明显下降。针刺显著改善MID大鼠空间记忆能力,提高其思维能力和分析判断能力;针刺还促进海马Glut1和Glut3表达,且具有腧穴特异性。结论:"益气调血,扶本培元"针法改善认知功能作用与调节脑血流,增强葡萄糖转运代谢等过程有关。  相似文献   

7.
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.  相似文献   

8.
A stimulatory effect of kaempferol 3-neohesperidoside ( 1) on glucose uptake (35% and 21%) was observed when the rat soleus muscle was incubated with 1 and 100 nM of this flavonoid glycoside, respectively. The concentration-response curve of insulin showed a stimulatory effect at 3.5 and 7.0 nM (42% and 50%) on glucose uptake when compared with the control group. The effect of 1 on glucose uptake was completely nullified by pretreatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and RO318220, an inhibitor of protein kinase C (PKC). However, no significant change occurred on glucose uptake stimulated by 1 when muscles were pretreated with PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and cycloheximide, an inhibitor of protein synthesis. Compound 1 and insulin (7 nM) did not show a synergistic effect on glucose uptake. Additionally, 100 mg/kg of 1 by oral gavage was able to increase glycogen content in the muscle. These results suggest that 1 stimulates glucose uptake in the rat soleus muscle via the PI3K and PKC pathways and, at least in part, independently of MEK pathways and the synthesis of new glucose transporters.  相似文献   

9.

Aim of the study

Cornus kousa F.Buerger ex Miquel, an oriental medicinal plant, has been traditionally used for the treatment of hyperglycemia, but its molecular mechanism remains unknown. The goal of this study was to investigate the peroxisome proliferator-activated receptor γ (PPARγ) ligand-binding activity of Cornus kousa and to determine the effects of Cornus kousa on insulin sensitization in 3T3-L1 cells for the treatment of type 2 diabetes.

Materials and methods

PPARγ luciferase transactivation assay was used to evaluate the PPARγ ligand-binding activity of Cornus kousa leaf extract. Western blot analysis, oil Red O staining, and glucose uptake assay were performed to evaluate PPARγ agonistic activity and insulin sensitizing effects of Cornus kousa leaf extract (CKE) in 3T3-L1 cells.

Results

CKE increased PPARγ ligand-binding activity in a dose-dependent manner. In addition, CKE enhanced adipogenesis and the expression of PPARγ target proteins, including glucose transporter 4 (GLUT4) and adiponectin, as well as proteins involved in adipogenesis, including PPARγ and CCAAT/enhancer binding protein α (C/EBPα) in 3T3-L1 adipocytes. Furthermore, CKE led to significant induction of glucose uptake and stimulated insulin signaling, but not to activation of AMP-activated protein kinase (AMPK) signaling. The enhanced glucose uptake by CKE were abolished by treatment with bisphenol a diglycidyl ether (BADGE), a PPARγ antagonist, or LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), but not by compound C, an AMPK inhibitor.

Conclusion

Consistent with the high PPARγ ligand-binding activity, CKE increased glucose uptake through PPARγ activation and insulin signaling. These results suggest that CKE could have pharmacological effects for the treatment of hyperglycemia and type 2 diabetes.  相似文献   

10.
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.  相似文献   

11.
Dysregulation of vesicle trafficking in muscle is one of the factors responsible for the pathogenesis of insulin resistance (IR). Ferulic acid (FER) and resveratrol (RSV) are known to have hypoglycemic property. In this study, differentiated L6 myotubes were induced with palmitate as a model of IR. Chemical ablation of muscle vesicles was used to investigate how FER and RSV influence glucose utilization. Results showed that both FER and RSV elicit glucose uptake and promote glycogen synthesis in insulin‐resistant muscle cells. Mechanistic studies further showed that FER markedly enhances the transferrin receptor‐containing endosomal compartment activities via phosphoinositide 3‐kinase (PI3K)/atypical protein kinase C‐dependent pathway, while RSV facilitates glucose transporter storage vesicles (GSV) trafficking via an exercise‐like effect of conventional protein kinase C/5′‐adenosine monophosphate‐activated protein kinase (AMPK) modulation. Therefore, these two phenolic compounds promoted glucose transport through two separate routes, and they had an additive effect on the increase of glucose uptake in insulin‐resistant muscle cells. These findings provide a basis for the understanding of the antidiabetic potential of RSV and FER combination.  相似文献   

12.
The hypoglycemic effect of the aqueous (Aq) extract of the bark of Pterocarpus marsupium (PM) and alcoholic (Alc) extract of seeds of Trigonella foenum-graecum (FG) and leaves of Ocimum sanctum (OS) was investigated in both normal and alloxan-induced diabetic rats. The Aq extract of PM (1 g/kg PO) significantly (P<0.001) reduced the blood sugar levels from 72.32+/-5.62 to 61.35+/-1.2 mg% 2 h after oral administration of the extract and also significantly lowered the blood glucose in alloxan diabetic rats from 202.91+/-5.44 to 85.22+/-11.28 mg% 21 days after daily oral administration of the extract (P<0.001). Similarly, reduction was seen with Alc extract of FG (74.33+/-4.77 to 60.56+/-1.9 in normal rats and 201.25+/-7.69 to 121.25+/-6.25 in diabetic rats) (P<0.001) and OS (204.48+/-11.0 to 131.43+/-7.86 in normal rats and 73.54+/-3.7 to 61.44+/-2.3 in diabetic rats) (P<0.001). In addition, the extract also showed a favorable effect on glucose disposition in glucose fed hyperglycemic rats.  相似文献   

13.
Long-term complications are frequently encountered in diabetes mellitus and are difficult to treat. This study was undertaken to assess the effect of three antidiabetic plants on the development of cataract in rats. An aqueous extract of Pterocarpus marsupium Linn bark (PM, Hindi name: Vijaysar) (1 g kg(-1) day(-1)), Ocimum sanctum Linn leaves (OS, Hindi name, Tulsi) (200 mg kg(-1) day(-1)) and alcoholic extract of Trigonella foenum-graecum Linn seeds (FG, Hindi name, Methi) (2 g kg(-1) day(-1)) were given to alloxan (120 mg kg(-1)) diabetic rats until the development of cataract. Serum glucose and body weight were monitored at regular intervals while cataract was examined through naked eye as well as slit lamp at 75, 100 and 115 days after alloxan administration. Administration of all the three plant extracts exerted a favorable effect on body weight and blood glucose, the effects were best with PM followed by FG and OS. On the course of cataract development, PM followed by FG exerted anti-cataract effect evident from decreased opacity index while OS failed to produce any anti-cataract effect in spite of significant antihyperglycemic activity.  相似文献   

14.

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.  相似文献   

15.
ETHNOPHARMACOLOGICAL RELEVANCE: The molecular mechanism of a traditional hypoglycemic Chinese herbal formula. AIM OF THE STUDY: To explore the glucose uptake effect as well as the mechanism(s) of action of Bai-Hu-Tang (BHT), a traditional Chinese herbal formula, composed of anemarrhena, gypsum, licorice and rice. MATERIALS AND METHODS: Differentiated 3T3-L1 adipocytes were treated with vehicle, insulin or insulin plus different concentrations of BHT. The 2-deoxy-[(3)H] glucose uptake assay was performed to measure the amount of glucose uptake. To explore the mechanism(s) of glucose uptake of BHT, we used two insulin signaling transduction inhibitors, N-Acetyl-Leu-Leu-Norleu-al (ALLN), a calpain inhibitor, and LY 294002, a phosphatidylinositol (PI)3-kinase inhibitor, to test if the glucose uptake effect was mediated by the insulin signaling pathway. We then used Western blot analysis to re-confirm the result of the insulin signaling inhibition assay. Finally, reporter chimera assay of HuH-7 cells was used to measure the peroxisome proliferator-activated receptor gamma (PPARgamma) activation by BHT. RESULTS: BHT potentiated insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The effect of BHT-stimulated glucose uptake was neither inhibited by ALLN nor by LY 294002. The protein expression of PI3 kinase pathway did not change after BHT stimulation. PPARgamma activation was elevated by 67.7+/-32% (p<0.05) in HuH-7 cells treated with 0.8 microg/ml of BHT. CONCLUSIONS: BHT stimulated glucose uptake in 3T3-L1 adipocytes. This effect was via PPARgamma activation rather than via the insulin signaling pathway.  相似文献   

16.

Ethnopharmacological relevance

Ophiopogon japonicus is a traditional Chinese medicine that might be helpful for the treatment of type 2 diabetes. Recent studies have confirmed its beneficial properties, but not the mechanism of action.

Aim of study

In this study, we examined the effects of a water-soluble β-d-fructan (MDG-1) from O. japonicus on type 2 diabetes through the PI3K/Akt pathway in a diabetic KKAy mouse model.

Materials and methods

MDG-1 was extracted from the tube root of O. japonicus and purified as described previously ( Xu et al., 2005). The KKAy mice were gavaged once daily with either distilled water, MDG-1or rosiglitazonefor 8 weeks. Blood glucose levels were tested regularly for the fed and fasted mice. In order to evaluate the effect of MDG-1 on disease progression, the proteins of InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 were detected by Western blotting and serum TG, TC, HDL-C, LDL-C were also dertermined.

Results

MDG-1 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia in the KKAy mice. The oral glucose tolerance test (OGTT) and the level of insulin in the serun showed that insulin resistance in KKAy mice was ameliorated after MDG-1 treated. After 8 weeks treatment with 300 mg/kg MDG-1, the content of triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) the serum decreased significantly. Meanwhile high density lipoprotein cholesterol (HDL-C) content increased notably. MDG-1 did not have any effect on total cholesterol (TC) content in the serum, whereas rosiglitazone significantly decreased the TC content. In addition, MDG-1 upregulates the phosphoinositide 3-kinase p85 subunit, Akt, insulin receptor (InsR), insulin receptor substrate-1 (IRS-1) and Glut-4 expression, but downregulates glycogen synthase kinase 3β expression.

Conclusions

These data indicate that MDG-1 has remarkable anti-diabetic activity through the InsR/IRS-1/PI3K/Akt/GSK-3/Glut-4 signaling pathway. We believe that MDG-1 is a promising anti-diabetic compound that will be helpful for the treatment of T2DM.  相似文献   

17.

Ethnopharmacological relevance

Walnut, Juglans regia L. (Juglandaceae), is one of the medicinal plants used to treat diabetic symptoms in Austrian folk medicine. The air-dried green leaves are either used as aqueous decoctions or liquor preparations and are consumed on a daily basis. We investigated the hypoglycemic effect of a methanolic Juglans regia leaf extract on glucose uptake, protein tyrosine phosphatase 1B (PTP1B) inhibition and peroxisome proliferator-activated receptor gamma (PPARγ) activation.

Material and methods

Hypoglycemic activity was assessed by glucose-uptake in C2C12 myocytes, inhibition of PTP1B and activation of PPARγ. Phytochemical characterization of the extract was carried out by LC–MS and GC–MS.

Results

Methanolic Juglans regia leaf extract enhanced the glucose uptake rate in C2C12 myocytes at concentrations of 25 µg/mL compared to untreated cells. This activity may partly be explained by the inhibition of PTP1B but not PPARγ agonism. LC–MS analyses revealed chlorogenic acid (1), 3-p-coumaroylquinic acid (2), a trihydroxynaphthalene-hexoside (3), as well as eight flavonoids (4–11) as main phenolic constituents in the active extract.

Conclusions

The finding that Juglans regia leaf extract enhances glucose uptake and inhibits PTP1B provides an in vitro-based rationale for the traditional use of walnut leaf preparations against elevated blood-glucose levels.  相似文献   

18.
Oleuropein, the main constituents of leaves and fruits of the olive tree, has been demonstrated to exert various therapeutic and pharmacological properties including antidiabetic effect. However, the effectiveness of oleuropein on glucose homeostasis in intact rat skeletal muscle ex vivo has never been explored. Therefore, our current study was carried out to investigate and confirm the beneficial effect of oleuropein (1.5 mM) on glucose uptake and on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle. For this purpose, soleus muscles were incubated for 12 hr without (control) or with oleuropein, in the presence or absence of AMP‐activated protein kinase (AMPK) inhibitor, compound C, or wortmannin, an inhibitor of phosphatidylinositol kinase. Oleuropein‐stimulated glucose transport, plasmalemmal glucose transporter 4 (GLUT4), and phosphorylation of phosphatidylinositol kinase and AMPK were examined. We observed that oleuropein treatment enhanced glucose transport, GLUT4 translocation, and AMPK phosphorylation. The oleuropein‐stimulated glucose uptake and GLUT4 translocation were inhibited by compound C and were not affected by wortmannin. These results suggest that increased glucose uptake induced by oleuropein might be mediated through activation of AMPK and the subsequent increase in GLUT4 translocation in skeletal muscles.  相似文献   

19.
The fluorescence shown by extracts of the heartwood of Pterocarpus marsupium is attributed to salts of the new compound 1, whose structure was elaborated using detailed spectroscopic/spectrometric studies. The plant material also contains the nonfluorescent compounds 2 and 3. The absolute configuration of 1 was determined by experimental and theoretically calculated electronic CD spectra, while that of 3 was deduced from ECD comparison with reported results in the α-hydroxydihydrochalcone series.  相似文献   

20.
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