MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model

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.     

Effects of water extract and crude polysaccharides from Liriope spicata var. prolifera on InsR/IRS-1/PI3K pathway and glucose metabolism in mice

Aim of the study

The present study was designed to investigate the effects of water extract (WE) and crude polysaccharides (CPs) from the tuberous root of Liriope spicata var. prolifer on the InsR/IRS-1/PI3K pathway and glucose metabolism in type 2 diabetic mice.

Materials and methods

WE and CPs were administered orally at different doses (200 and 100 mg/kg body weight) to streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice, respectively. After 4 weeks of administration, immunohistochemistry and western blot were applied to detect the expression levels of insulin receptor-α (InsR-α), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) in renal tissues of mice. Moreover, the hepatic glycogen content, glucokinase (GK) and glucose-6-phosphatase (G6Pase) activities were measured to investigate the effect of WE and CPs on glucose metabolism.

Results

Compared with diabetic control, greater immunostaining for InsR-α, IRS-1 and PI3K was present in the tubulointerstitial regions of WE and CPS groups in renal tissues and the expression levels of these three signal molecules from WE and CPs groups were significantly increased; the glycogen content and GK activity from WE and CPs groups in liver were significantly increased, yet the G6Pase activity was significantly lower.

Conclusions

It is demonstrated that WE and CPs can ameliorate insulin signaling transduction and glucose metabolism, as a result, lessen IR and hyperglycemia eventually. So, this study has provided more powerful evidences for Liriope spicata var. prolifer to be a potential hypoglycemic agent and insulin sensitizer.     

Regulation effects on abnormal glucose and lipid metabolism of TZQ-F,a new kind of Traditional Chinese Medicine

Aim of the study

Based on the recipe of the traditional anti-diabetic formula TZQ, we developed TZQ-F, a new formula including 8 fractions isolated from Red Paeony root, Mulberry leaf, Lotus leaf, Danshen root and Hawthorn leaf with a good quality assurance. The study was aimed at fraction preparation and effects of the fractions on abnormal glucose and lipid metabolism.

Materials and methods

The active fractions were obtained by macroporous resin, ion-exchange resin and polyamide resin column chromatographies. HPLC analyses were used for quality control. In vitro mechanism study included DPPH radical scavenging, AGEs formation inhibition, α-glucosidase inhibition and lipase inhibition, and rats on high-fat diet were used for in vivo study.

Results

In vitro mechanism study showed that among the 8 fractions, three of them had inhibition effects on intestinal disaccharase, three with inhibition effects on lipase, and five with effects of free radical scavenging. In vivo study showed that after 4 weeks of treatment, TZQ-F significantly decreased the levels of serum total cholesterol, TG, glucose, LDL-C and HDL-C in rats on high-fat diet. Consistent with the in vitro and in vivo results, histology study demonstrated that TZQ-F alleviated hepatic steatosis induced by high-fat diet.

Conclusions

TZQ-F possesses the potential regulation effects on abnormal glucose and lipid metabolism.     

Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPARγ and PI3K

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.     

TG accumulation inhibitory effects of Jinqi formula by AMPK signaling pathway

Ethnopharmacological relevance

Jinqi formula is a traditional Chinese anti-diabetic formula containing three ingredients (Coptidis rhizoma, Astragali rhadix and Lonicerae japonicae Flos).

Materials and methods

The active fractions of Jinqi formula were purified and HPLC analyses were used for quality control. The anti-adipogenic effects of Jinqi formula were analyzed in vitro using 3T3-L1 cells and in vivo with KK-A^y mice. RT-PCR and Western blot were used to confirm genes and proteins of interest, respectively.

Results

In vitro study showed that Jinqi formula suppressed the accumulation of triglyceride (TG) and free fatty acids (FFA) in mature 3T3-L1 cells by increasing the expression and tyrosine phosphorylation of 5′-AMP-activated protein kinase (AMPK), as well as decreasing the expression of Acetyl CoA Carboxylase (ACC), Fatty Acid Synthase (FAS) and Hormone Sensitive Lipase (HSL). In vivo study demonstrated that Jinqi formula reduced body weight without changing food intake in KK-A^y mice, and decreased the levels of serum glucose, TG, FFA. In addition, consistent with the in vitro study results, Jinqi formula increased the expression and tyrosine phosphorylation of AMPK in the liver and muscular tissues of the KK-A^y mice. Furthermore, Jingqi formula suppressed the expression of ACC and HSL and upregulated the expression of IRS-1 in the liver. Whereas in the skeletal muscles, Jingqi formula decreased the expression of ACC and increased the expression of GLUT-4 and IRS-2.

Conclusions

Jingqi formula inhibits TG accumulation at least in part via the stimulation of AMPK activity in a multi-target manner.     

黄连解毒汤对胰岛素抵抗大鼠脂肪组织胰岛素受体及其底物信号转导的影响

目的观察黄连解毒汤对胰岛素抵抗大鼠脂肪组织中胰岛素受体（InsR）酪氨酸磷酸化和胰岛素受体底物1（IRS-1）表达及其酪氨酸磷酸化水平的影响,探讨其改善胰岛素抵抗的分子机制。方法采用小剂量链脲佐菌素尾静脉注射加高糖高脂饲料喂养方法建立Wistar大鼠胰岛素抵抗模型,以黄连解毒汤干预治疗10周,检测血糖和血清胰岛素,用免疫沉淀和Westernblot方法检测黄连解毒汤治疗后胰岛素抵抗大鼠附睾脂肪组织内InsR酪氨酸磷酸化和IRS-1蛋白表达水平及酪氨酸磷酸化水平。结果黄连解毒汤治疗胰岛素抵抗大鼠后,脂肪组织内IRS-1表达较模型组增加,InsR和IRS-1酪氨酸磷酸化水平较模型组显著增加。结论黄连解毒汤促进胰岛素抵抗大鼠脂肪组织InsR和IRS-1酪氨酸磷酸化水平的表达,这可能是其降血糖并改善组织胰岛素敏感性的机制之一。     

Cyclocarya paliurus extract modulates adipokine expression and improves insulin sensitivity by inhibition of inflammation in mice

Ethnopharmacological relevance

Cyclocarya paliurus Batal., a Chinese native plant, is the sole species in its genus and its leaves have been widely used as a remedy for diabetes in traditional folk medicine. The study was undertaken to evaluate the effects of Cyclocarya paliurus leaves extracts (CPE) on adipokine expression and insulin sensitivity in mice.

Materials and methods

Mice were stimulated with conditioned medium (prepared from activated macrophages, Mac-CM) to induce adipose dysfunction and insulin resistance. Then mice were treated with CPE (100, 200 and 500 mg/kg, ig.) or metformin (200 mg/kg, ig.), followed by glucose and insulin intolerance, adipokine expression, phosphorylation of insulin receptor substrate (IRS-1) and glucose consumption measurement.

Results

CPE, as well as metformin effectively promoted glucose disposal in oral glucose tolerance test in normal mice. Mac-CM challenge induced glucose and insulin intolerance, but CPE reversed these alternations with increased glycogen content in muscle and liver, well demonstrating its beneficial effects on glucose homeostasis. RT-qPCR analysis showed that CPE inhibited TNF-a, IL-6, MCP-1 and resistin overexpression and effectively enhanced adiponectin expression in adipose tissue when mice were exposed to Mac-CM stimulation. Inflammation impaired insulin signaling in muscle, whereas CPE inhibited inflammation-induced serine phosphorylation of IRS-1 and effectively restored the phosphorylation of both IRS-1 at tyrosine residues and downstream Akt phosphorylation in response to insulin. Moreover, independently of insulin, CPE promoted glucose consumption in adipocytes under normal and inflammatory conditions.

Conclusion

Above-mentioned results demonstrated that CPE beneficially regulated adipokines expression and ameliorated insulin resistance through inhibition of inflammation in mice.     

Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats

Aim of the study

We investigated the preventive effect of Momordica charantia Linn. (Cucurbitaceae) fruit, commonly known as bitter melon, on hyperglycemia and insulin resistance in rats fed with a fructose-enriched diet.

Materials and methods

First, rats were divided randomly into two groups: the control group was fed with control diet, whereas the experimental group was fed with a 60% high-fructose diet for 8 weeks. After the first 6 weeks, the fructose-treated rats were further subdivided into six groups and were orally fed with or without Momordica charantia L. or rosiglitazone (ROS) for 2 weeks while rats were still on fructose diet.

Results

We demonstrated that bitter melon was effective in ameliorating the fructose diet-induced hyperglycemia, hyperleptinemia, hyperinsulinemia, and hypertriglyceridemia as well as in decreasing the levels of free fatty acid (FFA) (P < 0.001, P < 0.05, P < 0.05, P < 0.05, P < 0.05, respectively). Bitter melon reversed fructose diet-induced hypoadiponectinemia (P < 0.05), which provides a therapeutic advantage to insulin resistance in improving insulin sensitivity. Additionally, bitter melon decreased the weights of epididymal (P < 0.05) and retroperitoneal white adipose tissue (WAT) (P < 0.05). Bitter melon increased the expression of peroxisome proliferator-activated receptor γ (PPARγ) in white adipose tissue (WAT). Conversely, bitter melon decreased the expression of leptin in WAT. Furthermore, we demonstrate that bitter melon significantly increases the mRNA expression and protein of glucose transporter 4 (GLUT4) in skeletal muscle.

Conclusions

This study demonstrates, for the first time, the beneficial effects of two different extracts of bitter melon on insulin resistance in rats fed a high-fructose diet thereby producing evidence of the role of changes in expression of PPARγ and GLUT4.     

Preventive effects of total flavonoids of Litsea coreana leve on hepatic steatosis in rats fed with high fat diet

Aim of the study

To evaluate the protective effects of total flavonoids of Litsea Coreana leve (TFLC) on rat high fat diet-induced hepatic steatosis model.

Materials and methods

Rats were given either a high fat diet alone or the same diet plus TFLC for 4 weeks.

Results

TFLC improved liver histology with reduced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as decreased the over accumulation lipids in serum and liver. TFLC increased serum levels of leptin and insulin, while decreased serum TNFα level in high fat diet fed rat. Furthermore, TFLC was found increased the expression of peroxisome proliferator-activated receptor α (PPARα) in high fat diet fed rat liver. These benefits were associated with increased superoxide dismutase (SOD) and decreased malondialdehyde (MDA) in high fat diet fed rat liver.

Conclusions

TFLC exerts protective effects against hepatic steatosis in rats fed with high fat diet possibly through its antioxidant actions, improving the adipocytokines release and increasing the expression of PPARα.     

Antidiabetic effects of Artemisia sphaerocephala Krasch. gum,a novel food additive in China,on streptozotocin-induced type 2 diabetic rats

Aim of the study

Since ancient times, practicians of traditional Chinese medicine have discovered that Artemisia sphaerocephala Krasch. (Asteraceae) seed powder was useful for the treatment of diabetes. Artemisia sphaerocephala Krasch. gum (ASK gum), which is extracted from seed powder of the plant, is a novel food additive favored by the food industry in China. The objective of this study was to determine the antidiabetic function of ASK gum on type 2 diabetes.

Materials and methods

Type 2 diabetic rat model was induced with high fat diet and low dose of streptozotocin (STZ). The effects of ASK gum on hyperglycemia, hyperlipemia, insulin resistance, and liver fat accumulation in type 2 diabetic rats were evaluated. The results were compared to those of normal rats and diabetic rats treated with metformin.

Results

The addition of ASK gum to the rats’ food supply significantly lowered fasting blood glucose, glycated serum protein, serum cholesterol, and serum triglyceride in type 2 diabetic rats, and significantly elevated liver glucokinase, liver glycogen, and serum high density protein cholesterol in the diabetic rats. ASK gum significantly reduced insulin resistance and liver fat accumulation of type 2 diabetes.

Conclusion

: Artemisia sphaerocephala Krasch. gum can alleviate hyperglycemia, hyperlipemia and insulin resistance of type 2 diabetes.     

Astragalus polysaccharide improves insulin sensitivity in KKAy mice: Regulation of PKB/GLUT4 signaling in skeletal muscle

Ethnopharmacological relevance

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus Bunge (Leguminosae) that has been used in traditional Chinese medicine for treating diabetes.

Aim of the study

To study the mechanisms by which APS ameliorates diabetes, we examined whether treatment with APS improves insulin sensitivity in insulin-resistant mice and whether this is associated with an improvement of dysregulated protein kinase B and glucose transporter 4 expressions in skeletal muscle.

Methods

APS (700 mg kg⁻¹ day⁻¹) or vehicle was administered to 12-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Changes in body weight, blood glucose level, insulin resistance index, and oral glucose tolerance were routinely evaluated. The expressions of protein kinase B and glucose transporter 4 in skeletal muscle tissues were determined with Western blot.

Results

KKAy mice developed persistent hyperglycemia, impaired glucose tolerance and insulin resistance. Insulin-stimulated protein kinase B phosphorylation and glucose transporter 4 translocation were significantly decreased in KKAy compared to age-matched C57BL/6J mice. APS treatment ameliorated hyperglycemia and insulin resistance. Although the content of protein kinase B and glucose transporter 4 in KKAy skeletal muscle were not affected by APS, insulin-induced protein kinase B Ser-473 phosphorylation and glucose transporter 4 translocation in skeletal muscle were partially restored by APS treatment. In contrast, APS did not have any effect on C57BL/6J mice.

Conclusions

These results indicate that APS can regulate part of the insulin signaling in insulin-resistant skeletal muscle, and that APS could be a potential insulin sensitizer for the treatment of type 2 diabetes.     

Sarcopoterium spinosum extract as an antidiabetic agent: In vitro and in vivo study

Ethnopharmacological relevance

Sarcopoterium spinosum (L.) sp., a common plant in the Mediterranean region, is widely used as an antidiabetic drug by Bedouin healers. However, the antidiabetic properties of Sarcopoterium spinosum had not been fully validated using scientific tools.

Aim of the study

To determine the effectiveness of Sarcopoterium spinosum extract as an antidiabetic agent in vitro and in vivo.

Materials and methods

RINm pancreatic β-cells, L6 myotubes, 3T3-L1 adipocytes and AML-12 hepatocytes were treated with an aqueous Sarcopoterium spinosum extract (0.001–10 mg/ml). The effect of the extract on specific physiological functions, including insulin secretion, pancreatic β-cell viability, GSK3β phosphorylation, lipolysis and glucose uptake was measured. In vivo studies were performed using KK-A^y mice, given the extract for several weeks. IPGTT was performed, and plasma insulin, FFA, food consumption and body weight were measured. In addition, diabetic KK-A^y mice were given a single dose of the extract, and IPGTT was performed.

Results

Sarcopoterium spinosum extract increased basal and glucose/forskolin-induced insulin secretion in RINm cells, and increased cell viability. The extract inhibited lipolysis in 3T3-L1 adipocytes, and induced glucose uptake in these cells as well as in AML-12 hepatocytes and L6 myotubes. GSK3β phosphorylation was also induced in L6 myotubes, suggesting increased glycogen synthesis. Sarcopoterium spinosum extract had a preventive effect on the progression of diabetes in KK-A^y mice. Catechin and epicatechin were detected in Sarcopoterium spinosum extract using hyphenated LC–MS/MS.

Conclusions

Sarcopoterium spinosum extract has effects that mimic those of insulin and provide the basis for antidiabetic activity of the extract.     

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.     

Polyphenols in Madhumega chooranam, a Siddha Medicine, ameliorates carbohydrate metabolism and oxidative stress in type II diabetic rats

Ethnopharmacological relevance

Present study was undertaken to demonstrate the mode of anti-diabetic action of a polyherbal Siddha Medicine, Madhumega chooranam (MMC).

Materials and methods

MMC was fractionated into phenolic (PMMC) and non-phenolic (NPMMC) portions in order to identify bioactive fraction. Study was performed in type II diabetic rats. Role of PMMC and NPMMC on liver glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucokinase and glycogen content were determined. Their role on superoxide dismutase, reduced glutathione and lipid peroxidation were investigated. In addition, their effects on GLUT4 and PPARγ gene expression were studied. Pancreas and liver histopathology was studied using hematoxylin and eosin stain.

Results

PMMC improved carbohydrate metabolism by decreasing glucose-6-phosphatase and fructose-1,6-bisphosphatase and increasing glucokinase and glycogen contents in diabetic rats liver. It alleviated oxidative stress by increasing superoxide dismutase, glutathione and decreasing lipid peroxidation content. PMMC up-regulated liver GLUT4 and PPARγ mRNA expression in comparison to the vehicle or NPMMC rats.

Conclusion

Madhumega chooranam mediates its anti-diabetic action through the inhibition of gluconeogenesis and activation of glycolytic pathways in type II diabetic rats. Increased GLUT4 and PPARγ expressions provide additional information on its glucose uptake/sensitising and hypolipidemic potential. Phenolic components of MMC were found to be the bioactive principles.     

补肾通脉方对胰岛素抵抗大鼠胰岛素信号转导的影响

目的：观察补肾通脉方对高脂饮食诱导的胰岛素抵抗(IR)模型大鼠肌肉和脂肪组织中胰岛素刺激后的胰岛素受体(InsR)和胰岛素受体底物-1(IRS-1)酪氨酸磷酸化的影响。方法：雄性Wistar大鼠随机分为正常组、模型组和治疗组,治疗组以纯中药制剂补肾通脉方进行干预;模型组和治疗组大鼠均用脂肪占总热卡含量61％的高脂饲料饲养8周,正常组喂以普通饲料;常规测定空腹血糖(FBG)及葡萄糖负荷后1、2h血糖(BG-1h,BG-2h),以放射免疫法测定空腹血清胰岛素(Fins);采用免疫沉淀及Western blot技术测其肌肉及脂肪组织中胰岛素刺激后的InsR和IRS-1酪氨酸磷酸化水平。结果：与模型组比较,治疗组FBG虽无明显变化,但Fins显著降低(P<0．01),因而胰岛素敏感指数(ISI)明显升高(P<0．01);治疗组BG-1h和BG-2h水平较模型组明显降低(P<0．05,P<0．01);治疗组大鼠肌肉和脂肪组织中InsRβ亚单位和IRS-1酪氨酸磷酸化蛋白电泳条带密度明显增加。结论：补肾通脉方对大鼠IR有显著的改善作用,其机制可能与提高IR大鼠肌肉和脂肪组织中InsR和IRS-1在胰岛素刺激后的酪氨酸磷酸化水平,改善胰岛素信号转导等环节有关。     

Cornus kousa F.Buerger ex Miquel increases glucose uptake through activation of peroxisome proliferator-activated receptor γ and insulin sensitization

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.     

The Korean traditional medicine Gyeongshingangjeehwan inhibits adipocyte hypertrophy and visceral adipose tissue accumulation by activating PPARα actions in rat white adipose tissues

Aim of the study

Gyeongshingangjeehwan (GGEx), which is a polyherbal drug composed of four medicinal plants, has traditionally been used as anti-obesity drug in Korean local clinics. Thus, we investigated the effects of GGEx on visceral adiposity and examined whether adipose peroxisome proliferator-activated receptor α (PPARα) activation is involved in this process.

Materials and methods

After Obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats and differentiated 3T3-L1 adipocytes were treated with GGEx, we studied the effects of GGEx on not only visceral white adipose tissue (WAT) mass and adipocyte size, but also the expression of adipocyte marker and PPARα target genes.

Results

Administration of GGEx to obese rats for 8 weeks decreased visceral WAT weight by 30% and the size of adipocytes in mesenteric WAT by 31% without weight changes of other organs. Concomitantly, GGEx increased mRNA levels of PPARα target genes responsible for fatty acid β-oxidation in mesenteric WAT whereas decreased mRNA expression of adipocyte markers, such as PPARγ, aP2 and leptin. Serological studies demonstrated that plasma levels of free fatty acids and triglycerides as well as insulin and glucose were decreased following GGEx treatment. Consistent with the in vivo data, GGEx increased PPARα reporter gene activity and induced the mRNA expression of PPARα target genes involved in mitochondrial fatty acid β-oxidation in 3T3-L1 cells. GGEx also inhibited triglyceride accumulation in these cells.

Conclusion

These results suggest that GGEx promotes the reductions in visceral fat mass and adipocyte size in obese animals, and that this event may be mediated by adipose PPARα activation.     

黄芪注射液对2型糖尿病动物模型KKAy小鼠肾损伤病理改变的影响

目的:从肾功能和肾组织形态变化观察黄芪对2型糖尿病动物模型KKAy小鼠肾脏病理改变的影响,研究黄芪对糖尿病肾病的有关作用机制.方法:雄性KKAy小鼠饲养至14周龄时随机分成模型组和黄芪治疗组(ip,3 mL·kg-1·d-1).同龄雄性C57BL/6J小鼠为正常对照组.分别于20,24,28周龄时检测各组小鼠血糖、血清肌酐和血尿素,光镜、电镜下观察各组小鼠不同周龄时的肾脏病理变化情况.结果:模型组KKAy小鼠从20周龄开始血糖、血尿素水平明显高于正常组小鼠(P＜0.01),24及28周龄时血清肌酐水平明显高于正常组小鼠(P＜0.01).黄芪治疗组KKAy小鼠从20周龄开始血糖明显高于正常组小鼠(P＜0.01),但低于模型组小鼠(P ＜0.05或P＜0.01);24及28周龄时血清肌酐水平明显低于模型组小鼠(P＜0.01);从20周龄开始血尿素水平明显低于模型组小鼠(P＜0.01),与正常组比较无明显差异.从20周龄开始模型组KKAy小鼠开始出现肾小球系膜区增宽,基底膜增厚,肾小管上皮细胞胞浆出现空泡,肾间质胶原结缔组织增多等病理变化,且随周龄增加病变加重;经黄芪注射液后治疗后的的KKAy小鼠,以上病变出现不同程度改善.结论:黄芪注射液能改善2型糖尿病KKAy小鼠肾功能,减轻肾脏病理损害,具有肾脏保护作用.     

Rhodiola crenulata root ameliorates derangements of glucose and lipid metabolism in a rat model of the metabolic syndrome and type 2 diabetes

Ethnopharmacological relevance

Rhodiola species are traditionally used as tonics and stimulants to treat asthenia, suggesting their possible regulatory effect on energy metabolism. Clinical trials have demonstrated their glucose-lowering effect in type 2 diabetes.

Aim of the study

To examine the effects of Rhodiola on glucose and lipid metabolism in the metabolic syndrome and type 2 diabetes.

Materials and methods

Zucker diabetic fatty (ZDF) rats were treated with Rhodiola crenulata root (RCR) powder (100 and 500 mg/kg, by gavage, once daily for 4 weeks). In addition, the effects of RCR on sucrose-induced acute hyperglycemia in mice and olive oil-induced hypertriglyceridemia in rats were also examined. Biochemical variables were determined enzymatically or by ELISA.

Results

In ZDF rats, RCR treatment decreased the increased plasma insulin and triglyceride concentrations at baseline, the index of the homeostasis model assessment of insulin resistance (HOMA-IR) and excessive hepatic triglyceride accumulation. This treatment also inhibited abnormal increases in plasma glucose and insulin concentrations during oral glucose tolerance test. Furthermore, RCR reversed the increased adipose insulin resistance index, and accelerated the decline of plasma concentrations of non-esterified fatty acids after exogenous glucose stimulation. However, RCR minimally affected sucrose-induced acute hyperglycemia in mice and olive oil-induced acute hypertriglyceridemia in rats.

Conclusions

The present results demonstrate that RCR treatment improves metabolic derangements in animal model of the metabolic syndrome and type 2 diabetes. Our findings may provide new pharmacological basis of therapeutics for the adaptogenic plants to treat metabolic derangements-associated disorders, such as asthenia.