红景天、蛹虫草、大黄配伍治疗代谢综合征的实验研究Ⅰ——改善胰岛素抵抗作用

探讨红景天、蛹虫草、大黄配伍(中药复方FF16)对小鼠胰岛素抵抗的治疗作用及其作用机制。结果显示,中药复方FF16具有明显增加机体整体和组织胰岛素敏感性作用;分别使IRF小鼠和KKAy小鼠的受损的胰岛素耐量之AUC降低24.1%,38.5%;升高的血清胰岛素水平下降46.0%,30.4%,HOMA-IR降低52.4%,81.2%;降低的GIR增加了119.3%,202.4%。FF16使KKAy小鼠全身胰岛素敏感性指数ISWBI增加了1.0倍;肝脏、脂肪和骨骼肌胰岛素依赖的葡萄糖摄取能力分别增强1.5,2.8,2.2倍。此外,FF16抑制基因重组人源蛋白酪氨酸磷酸酶(PTP1B)蛋白活性的IC50为0.225 mg.L-1;使IRF小鼠肝脏升高的蛋白PTP1B表达下调了45.8%。结果说明,中药复方FF16具有显著的胰岛素增敏作用,该作用可能与抑制PTP1B活性有关。     

Improvement of Insulin Resistance by Chlorella in Fructose‐rich Chow‐fed Rats

Chlorella is a type of unicellular fresh water algae. In an attempt to develop new agents for handling insulin resistance, Chlorella was employed to screen the effect on insulin resistance in rats induced by fructose‐rich chow. A single oral administration of Chlorella for 90 min decreased the plasma glucose in a dose‐dependent manner in rats receiving 4‐week fructose‐rich chow. In addition, chronic treatment with Chlorella for 15 days also lowered plasma glucose in the same manner. Then, the insulin action on glucose disposal rate was measured using the glucose‐insulin index, values of the areas under the curves of glucose and insulin during the intraperitoneal glucose tolerance test (IPGTT). Oral administration (three times daily for 5 days) of Chlorella to rats receiving 4 weeks of fructose‐rich chow abolished the elevated value of the glucose‐insulin index, indicating that Chlorella has an ability to improve insulin resistance. An increase of insulin sensitivity by Chlorella was further evaluated using the plasma glucose lowering action of exogenous insulin in streptozotocin‐induced diabetic rats (STZ‐diabetic rats). Oral administration of Chlorella three times daily to STZ‐diabetic rats increased the response to exogenous insulin 15 days later. The obtained results suggest that oral administration of Chlorella has the ability to improve insulin sensitivity, which may be used as an adjuvant therapy for patients with insulin resistance. Copyright © 2011 John Wiley & Sons, Ltd.     

Effect of Sutherlandia frutescens on the Lipid Metabolism in an Insulin Resistant Rat Model and 3T3‐L1 Adipocytes

High fat diet induced insulin resistance correlates with dyslipidaemia and ectopic fat deposits in skeletal muscle and liver. The effects of Sutherlandia frutescens, an antidiabetic medicinal plant, on lipid metabolism were evaluated in an insulin resistant (IR) rat model and in 3 T3‐preadipocytes. Wistar rats received normal diet (ND) or high fat diet (HFD). After the onset of IR in the HFD group, the rats were subdivided into two subgroups, which either continued with HFD or were treated with 50 mg S. frutescens/kg BW/day and HFD (HFD + SF). After 4 weeks, the HFD + SF rats had a significantly lower body weight than the HFD rats (p < 0.05). Blood plasma analysis showed a decrease in insulin, free fatty acids and triglycerides. Related changes in lipid parameters were observed in the liver, skeletal muscle and adipose tissue. To investigate the effects of S. frutescens on adipose tissue, 3 T3‐L1 cells were used as a model. Treatment with S. frutescens led to a decrease in triglyceride accumulation, whilst glucose consumption and lactate production were increased (p < 0.05). These results indicate that S. frutescens directly affects mitochondrial activity and lipid biosynthesis in adipose tissue and provide a mechanism by which S. frutescens can restore insulin sensitivity by modulating fatty acid biosynthesis. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

The functional assessment of Alpinia pricei on metabolic syndrome induced by sucrose‐containing drinking water in mice

This study was designed to test whether Alpinia pricei (AP), a member of the ginger family indigenous to Taiwan, reduced metabolic syndrome induced by sucrose‐containing drinking water in C57BL/6J mice. Mice given a chow diet were divided into a control group (C) or a test group given 30% sucrose water (SW) to drink ad libitum. After 22 weeks, mice in the SW group were subdivided into SW and SW + AP groups, the latter receiving a chow diet with an ethanol extract of AP (1500 mg/kg dosage). Four weeks later, bio‐indexes associated with metabolic syndrome were measured. Compared with the C group, the SW group had significantly higher body weight, visceral fat weights, serum and tissue lipid, serum insulin level and the area under the curve for blood glucose of the insulin tolerance test (p < 0.05). These indicators in the SW + AP group were lower than in the SW group except for serum lipid, although slightly higher than the C group. The SW + AP group also showed significantly lower serum levels of leptin and tumor necrosis factor‐α and a significantly higher level of adiponectin than the SW group. These results indicated that visceral adiposity and insulin resistance induced by sucrose water drinking might be alleviated by AP supplementation. Copyright © 2008 John Wiley & Sons, Ltd.     

Improvement on lipid metabolic disorder by 3'-deoxyadenosine in high-fat-diet-induced fatty mice

This study explores the effects of 3'-deoxyadenosine, a compound from Cordyceps militaris, on lipid metabolic disorder induced by a high-fat-diet in C57BL/6 mice. These mice had an obese body, lipid metabolic disorder and insulin resistance and were treated orally with 100 mg/kg/day 3'-deoxyadenosine (DA), 15 mg/kg/day rosiglitazone and 150 mg/kg/day fenofibrate, respectively. Compared to the model mice, the body weight gain in DA-treated mice were decreased by 66.5%, serum triglyceride and total cholesterol levels were decreased by 20.7% and 16.7%, respectively, and the triglyceride content in the skeletal muscle was reduced by 41.2%. This treatment also had a significant effect on insulin resistance. In DA-treated mice, the serum insulin levels and homeostasis model assessment of the insulin resistance index were decreased by 30% and 46%, respectively, and the areas under the glucose-time curve were depressed by 18% in the insulin tolerance test and by 21.5% in the oral glucose tolerance test. Finally, the value of glucose infusion rates and insulin induced-glucose uptake into the skeletal muscle in the hyperinsulinemic-euglycemic clamp test were increased by 18% and 41%, respectively, compared to those in the model mice. This data suggests that the effects of DA on lipid metabolic disorder induced by a high-fat-diet may be linked to its improvement on insulin resistance, especially concerning the increase of insulin sensitivity in the skeletal muscle.     

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.     

Anti‐Hyperglycemic Effect of Fermented Ginseng in Type 2 Diabetes Mellitus Mouse Model

Ginseng has shown an efficacy in preventing and managing various health conditions. This study aimed to evaluate the effect of the fermented ginseng extract (FGE) in type 2 diabetes mellitus murine model. FGE was provided to male C57BL/ksJ‐db/db mice for 8 weeks at 0.1% (w/w) dose in contrast to water for the control group. Potential anti‐diabetic mechanisms were investigated with blood glucose, serum insulin, serum adiponectin, hemoglobin A1c (HbA1c), glucose tolerance, insulin secretion assay, quantitative real‐time polymerase chain reaction, and hematoxylin–eosin staining. Compared with the control group, the FGE group had lower levels of blood glucose after 6 and 9 h fasting, HbA1c, and the area under the curve in an oral glucose tolerance test and higher levels of adiponectin and serum insulin (p < 0.05). The FGE group had higher levels of peroxisome proliferator‐activated receptor gamma 2 and glucose transporter protein 2 mRNAs, a lower level of tumor necrosis factor‐α (TNF‐α) (p < 0.05), and less lymphocytes in pancreas than the control group had. The FGE exerted anti‐diabetic effects in type 2 diabetic mice. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of Water Extracts from Edible Myrtaceae Plants on Uptake of 2‐(n‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino)‐2‐deoxyglucose in TNF‐α‐Treated FL83B Mouse Hepatocytes

This study investigated the glucose uptake activity of the water extracts from the leaves and fruit of edible Myrtaceae plants, including guava (Psidium guajava Linn.), wax apples [Syzygium samarangense (Blume) Merr. and L.M. Perry], Pu‐Tau [Syzygium jambo (L.) Alston], and Kan‐Shi Pu‐Tau (Syzygium cumini Linn.) in FL83B mouse hepatocytes. The fluorescent dye 2‐(n ‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino)‐2‐deoxyglucose was used to estimate the uptake ability of the cells. Glucose uptake test showed that pink wax apple fruit extract (PWFE) exhibits the highest glucose uptake activity, at an increment of 21% in the insulin‐resistant FL83B mouse hepatocytes as compared with the TNF‐α‐treated control group. Vescalagin was isolated using column chromatography of PWFE. This compound, at the concentration of 6.25 µg/mL, exhibits the same glucose uptake improvement in insulin‐resistant cells as PWFE at a 100‐µg/mL dose. We postulate that vescalagin is an active component in PWFE that may alleviate the insulin resistance in mouse hepatocytes. Copyright © 2012 John Wiley & Sons, Ltd.     

Cortex Lycii Radicis extracts improve insulin resistance and lipid metabolism in obese‐diabetic rats

Here we evaluate the effects of ethanol and aqueous extracts from Cortex Lycii Radicis (CLR) on insulin resistance and lipid metabolism in obese‐diabetic rats, which were induced by high fat feeding for 3 weeks after injection with streptozotocin (STZ). Diabetic rats treated with ethanol or aqueous extracts of CLR at 15 and 30 g/kg dosage for 7 weeks, had decreased body weights, concentration of serum glucose, triglyceride (TG), total cholesterol (TC), and low‐density lipoprotein‐cholesterol (LDL‐C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), while the insulin‐sensitivity index (ISI) improved significantly compared with the control group. In addition, high contents of tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and low adiponectin level were observed in the control group and levels of TNF‐α and IL‐6 in CLR groups showed obvious differences with the control group. Histopathologic examination also showed degrees of hepatocyte edema although hepatocyte ballooning degeneration was lessened in all CLR groups. Overall, ethanol extract from CLR seemed to be more effective than aqueous extracts in improving insulin resistance, resulted in elevating insulin sensitivity, adjusting glucose and lipid metabolism, correcting cytokines levels and ameliorating liver function, especially protecting the liver against lipoid degeneration. Copyright © 2008 John Wiley & Sons, Ltd.     

菩人丹对ob/ob小鼠糖脂代谢及胰岛素抵抗的影响

[目的]考察菩人丹对肥胖小鼠糖脂代谢及胰岛素抵抗的影响,为中药复方菩人丹调节糖脂代谢的临床应用提供实验依据。[方法]将ob/ob小鼠随机分为模型组和菩人丹组,后者给予菩人丹干预15周,以C57BL/6J为空白组。测定小鼠空腹体质量、内脏脂肪指数、空腹血糖(FPG)、空腹血清胰岛素(FINS)及血脂水平,计算稳态模型胰岛素抵抗指数(HOMA-IR)及胰岛素敏感指数(ISI),评价胰岛素抵抗与分泌水平,口服葡萄糖耐量试验(OGTT)考察ob/ob小鼠对葡萄糖的耐受性;苏木精-伊红(HE)染色观察睾周脂肪细胞形态。[结果]模型组ob/ob小鼠的空腹体质量、内脏脂肪指数、OGTT曲线下面积、血脂水平与HOMA-IR均显著升高,ISI显著下降;菩人丹对ob/ob小鼠空腹体质量、内脏脂肪指数及糖耐量的影响无统计学意义;菩人丹能够降低ob/ob小鼠血清中总胆固醇(TC)、低密度脂蛋白(LDL)及HOMA-IR,升高ISI,同时使ob/ob小鼠睾周脂肪细胞排列相对规则有序。[结论]经15周观测,模型组ob/ob小鼠已形成肥胖、血脂紊乱、糖耐量损伤以及胰岛素抵抗,糖尿病前期模型复制成功;菩人丹有效改善了ob/ob小鼠糖脂代谢紊乱,增强了胰岛素敏感性,降低了胰岛素抵抗程度,表明菩人丹对糖尿病前期向2型糖尿病发展有确切的干预效果。     

Anti‐diabetic and Anti‐hyperlipidemic Effects and Safety of Salacia reticulata and Related Species

Extracts of Salacia reticulata Wight (Hypocrataceae) roots, stems, and leaves have been used in Asia for hundreds of years for the folkloric treatment of diabetes and other health problems. Constituents that have been identified as exhibiting anti‐diabetic effects include salacinol, kotalanol, ponkorinol, salaprinol, and their corresponding de‐0‐sulfonated compounds. Mangiferin, kotalagenin 16‐acetate and various proanthocyanidin oligomers have also been isolated. Studies indicate that Salacia extracts modulate multiple targets that influence carbohydrate and lipid metabolism including α‐glucosidase, aldose reductase, pancreatic lipase, peroxisomal proliferator‐activated receptor‐α, glucose transporter‐4 mediated glucose uptake, and angiotensin II type 1 receptor. Furthermore, Salacia extracts exhibit free radical scavenging, antioxidant and hepatoprotectant activities. In human studies, Salacia extracts have been shown to decrease plasma glucose and insulin levels, decrease HbA1c, and modulate serum lipid levels with no adverse effects being reported. Similar results have been demonstrated in rat and mouse models as well as in vitro systems. Safety of S. reticulata and other Salacia species as S. oblonga and S. chinensis in rats and mice indicate that extracts are exceedingly safe. No clinical studies have examined the effects of Salacia extracts on human weight loss, although weight loss and decreases in weight gain have been demonstrated in animal models. Because of the large number of pharmacologically active compounds, it is difficult to establish standards for extracts. © 2015 The Authors. Phytotheraphy Research published by John Wiley & Sons Ltd.     

Potent Effects of the Total Saponins from Dioscorea nipponica Makino Against Streptozotocin‐Induced Type 2 Diabetes Mellitus in Rats

The aim of the present paper was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against type 2 diabetes mellitus. Streptozotocin (STZ) with high‐fat diet induced type 2 diabetes mellitus (T2DM) rats were treated with TSDN. Some biochemical parameters, target proteins and genes were investigated. The results showed that TSDN decreased the levels of food/water intake, fasting blood glucose and serum lipid parameters, ameliorated oral glucose and insulin tolerance test levels, markedly increased body weight and serum insulin, reduced excess free radicals and affected ossification and renal protection. Histopathological examination indicated that TSDN increased liver glycogen, decreased the production of lipid vacuoles and lightened liver damage. Further investigation showed that TSDN down‐regulated the protein expressions of NF‐κB, GRP78, ATF6, eIF2 and the levels of MAPK phosphorylation and up‐regulated the protein expressions of IRS‐1, GLUT‐4, p‐Akt and p‐AMPK. In addition, TSDN obviously decreased the gene expressions of TNF‐a, IL‐6, PEPCK, G6Pase, GSK‐3β and GSK‐3β activity, and increased the gene expressions of PFK, PK and GK activity. These findings show the anti‐diabetic activity of total saponins from D. nipponica Makino, which should be developed as a new potent drug for treatment of diabetes mellitus in future. Copyright © 2014 John Wiley & Sons, Ltd.     

黄芪葛根汤对实验性糖尿病及胰岛素抵抗的影响

目的:观察黄芪葛根汤对实验性糖尿病及胰岛素抵抗(IR)的影响。方法:建立链脲佐菌素(STZ)ip所致糖尿病小鼠模型,sc氢化可的松琥珀酸钠(HCSS)诱导的IR小鼠模型,以及采用给大鼠1次ip小剂量链脲佐菌素(STZ),并加饲高热量饮食(富含脂肪和蔗糖),制备2型糖尿病(T2DM)伴胰岛素抵抗(IR)大鼠模型,观察黄芪葛根汤对糖脂代谢以及IR的影响。结果:黄芪葛根汤降低糖尿病小鼠的空腹血糖(FBG),提高糖耐量(OGTT),改善小鼠对胰岛素的敏感性。黄芪葛根汤能显著降低2型糖尿病胰岛素抵抗大鼠的FBG,提高OGTT,降低高胰岛素水平,提高胰岛素耐量,增加胰岛素敏感指数(ISI)和降低IR指数(HOMA-IR)指数。同时,黄芪葛根汤还可调节血脂、下调血清中游离脂肪酸(FFA)的水平。结论:黄芪葛根汤通过改善糖脂代谢、提高胰岛素的敏感性,发挥其治疗糖尿病及胰岛素抵抗的作用。     

人参皂苷Rb1改善高脂喂养肥胖小鼠胰岛素抵抗和脂肪异位沉积

人参皂苷Rb₁是人参的主要活性成分,前期体外实验显示人参皂苷Rb₁能够抑制脂肪细胞脂肪分解和促进葡萄糖转运的作用。本研究利用高脂饮食诱导的肥胖小鼠,研究人参皂苷Rb₁对胰岛素抵抗和脂肪异位沉积的影响及其作用的分子机制。将高脂喂养的肥胖雄性C57/L小鼠,随机分为高脂组（DIO组）,人参皂苷Rb₁组（Rb₁组）和罗格列酮组（Rog组）,继续给予高脂饲料喂养,另设立正常饲料喂养的C57/L小鼠为正常组（NC组）;分别按20,10 mg·kg^-1体重给予Rb₁组和Rog组小鼠每天腹腔注射人参皂苷Rb₁和罗格列酮,NC组和DIO组以等量的生理盐水腹腔注射。治疗2周后,进行腹腔注射葡萄糖耐量试验（IPGTT）,3 d后,处死小鼠,留取血清,检测胰岛素、游离脂肪酸（FFA）及生化指标;称取肝脏质量,检测肝脏内甘油三酯含量和病理检测;称取附睾脂肪质量,蛋白印迹检测PDE3B,HSL,周脂素。结果显示人参Rb₁治疗2周明显改善肥胖小鼠的葡萄糖耐量,除了0~120 min,Rb₁组葡萄糖耐量曲线下面积（0~30,0~60,0~90 min）较DIO组均显著下降（P<0.05,n=5）,胰岛素抵抗指数（HOMA-IR）显著下降（P<0.05,n=5）;并且Rb₁显著降低了肥胖小鼠肝脏内的脂肪水平（P<0.05,n=5）,肝脏质量/体重也明显下降（P<0.05,n=8）;Rb₁治疗后,肥胖小鼠血中升高的FFA水平也明显下降（P<0.05,n=8）;附睾脂肪中周脂素表达水平得到部分恢复,但对PDE3B的表达以及HSL的表达和磷酸化激活未见明显影响。以上研究结果表明人参皂苷Rb₁能够通过上调脂肪组织周脂素的表达,减少游离脂肪酸的释放和甘油三酯的异位沉积,这可能是其改善机体胰岛素抵抗和糖代谢异常的作用机制之一。     

降糖消渴颗粒对2型糖尿病大鼠糖脂代谢的影响

目的： 探讨肝脾肾同治的组方降糖消渴颗粒对2型糖尿病大鼠糖脂代谢的影响。方法： SD大鼠高脂饲料喂养4周后结合腹腔注射链脲佐菌素（STZ）30 mg·kg^-1,建立2型糖尿病大鼠模型,将成模的大鼠按血糖随机分为模型组、阳性对照组（二甲双胍0.2 g·kg^-1）、降糖消渴颗粒高、中、低剂量组（按生药量计为17.6,8.8,4.4 g·kg^-1）,并设正常对照组。干预4周后,观察治疗期间大鼠的一般情况,检测大鼠空腹血糖、血脂、空腹血清胰岛素、糖化血红蛋白及糖耐量、胰岛素耐量。结果： 降糖消渴颗粒可降低糖尿病模型大鼠体重（P<0.05）,与模型组相比,可降低空腹血糖（P<0.05）,使胰岛素敏感指数水平升高（P<0.05）,糖化血红蛋白与模型组比较有一定的改善,但差异无统计学意义。而血清胰岛素水平、血脂水平未见明显变化。给药后大鼠的糖耐量得以改善（P<0.05）,且呈现良好的时-效关系。胰岛素耐量实验显示降糖消渴颗粒各剂量组均具有一定的增强胰岛素敏感性的作用。结论： 立足于肝、脾、肾三脏同治的中药复方降糖消渴颗粒能改善2型糖尿病大鼠糖、脂代谢及胰岛功能,其改善2型糖尿病胰岛素抵抗可能是其防治糖尿病的机制之一。     

白术多糖对自发性2型糖尿病小鼠血糖及相关指标的影响

目的:观察白术多糖对自发性2型糖尿病db/db小鼠的降血糖作用。方法:以db/db 2型糖尿病小鼠为研究对象,分为模型组、阳性药组(盐酸二甲双胍250 mg·kg-1)、白术多糖3个剂量组(300,90,30 mg·kg-1),连续ig给予相应药物4周。给药期间观察小鼠的一般体征及体重,于给药第2,4周检测空腹血糖(FBG);给药4周后,检测小鼠空腹血浆胰岛素(Ins)以及口服糖耐量(OGTT)的变化,并根据血糖计算胰岛素敏感性指数(ISI)。结果:与模型组相比,白术多糖(300,90 mg·kg-1)给药期间db/db小鼠整体状态较好,毛色较光滑,饮食饮水量降低,明显降低db/db小鼠空腹血糖、血浆胰岛素,升高胰岛素敏感性指数,降低小鼠在给予葡萄糖后各个时间点(0.5,2 h)血糖值及血糖曲线下面积(AUC),(P0.05,P0.01);但对体重无明显影响。结论:白术多糖能够有效降低db/db 2型糖尿病小鼠的空腹血糖,降低血浆胰岛素水平,增加胰岛素敏感性指数,改善糖耐量,其降糖作用机制之一可能是通过降低血浆胰岛素、增加胰岛素的敏感性。     

Insulin‐Sensitizing and Beneficial Lipid‐Metabolic Effects of the Water‐Soluble Melanin Complex Extracted from Inonotus obliquus

Inonotus obliquus has been traditionally used for treatment of metabolic diseases; however, the mechanism remains to be elucidated. In this study, we found that the water‐soluble melanin complex extracted from I. obliquus improved insulin sensitivity and reduced adiposity in high fat (HF)‐fed obese mice. When the melanin complex was treated to 3T3‐L1 adipocytes, insulin‐stimulated glucose uptake was increased significantly, and its phosphoinositide 3‐kinase‐dependent action was proven with wortmannin treatment. Additionally, dose‐dependent increases in Akt phosphorylation and glucose transporter 4 translocation into the plasma membrane were observed in melanin complex‐treated cells. Adiponectin gene expression in 3T3‐L1 cells incubated with melanin complex increased which was corroborated by increased AMP‐activated protein kinase phosphorylation in HepG2 and C2C12 cells treated with conditioned media from the 3T3‐L1 culture. Melanin complex‐treated 3T3‐L1 cells showed no significant change in expression of several lipogenic genes, whereas enhanced expressions of fatty acid oxidative genes were observed. Similarly, the epididymal adipose tissue of melanin complex‐treated HF‐fed mice had higher expression of fatty acid oxidative genes without significant change in lipogenic gene expression. Together, these results suggest that the water‐soluble melanin complex of I. obliquus exerts antihyperglycemic and beneficial lipid‐metabolic effects, making it a candidate for promising antidiabetic agent. Copyright © 2014 John Wiley & Sons, Ltd.