El tejido adiposo, ¿solo un almacén de energía? / Adipose Tissue, Just an Energy Storage?

Resumen Cuando los alimentos cubren los requerimientos energéticos, el organismo almacena el exceso de calorías como glucógeno en el hígado y el músculo, y los triacilgliceroles en el tejido adiposo. Morfológica y funcionalmente se clasifica en blanco y pardo. El pardo tiene gran cantidad de mitocondrias, almacena los triacilgliceroles en vacuolas y disipa la energía en forma de calor; el blanco almacena energía en gotas lipídicas que ocupan la mayor parte de su volumen. Después de la ingesta de alimentos se libera insulina, lo que hace que externen GLUT4 para absorber glucosa. Los quilomicrones o las lipoproteínas de muy baja densidad (VLDL) transportan los triacilgliceroles a los depósitos de tejido adiposo. Durante el ayuno, por acción del glucagón, se liberan enzimas que degradarán a los tri, di y monogliceroles para liberar a los ácidos grasos. El tejido adiposo libera citocinas pro y antiinflamatorias, así como leptina, adiponectina que regulan el apetito y la saciedad. La proteína cinasa activada por AMP se activa como respuesta a una baja en la cantidad de energía de la célula y le ayuda a mantener un balance energético. En el adipocito promueve la degradación de los triacilgliceroles para liberar a los ácidos grasos que se emplearán como fuente energética. Se requiere de mayor cantidad de estudios para conocer más sobre la función del tejido adiposo como regulador del metabolismo y no solo como almacén de energía.

Abstract When food meets energy requirements, the body stores in the liver and in the muscle the excess of calories as glycogen and triacylglycerols in the adipose tissue. Morphologically and functionally, it is classified into white and brown tissues. Brown tissue has many large mitochondria and stores triacylglycerols in vacuoles and dissipates energy as heat; white tissue stores energy as lipid droplets that occupy most of the adipocyte's volume. After food intake insulin is released, which causes GLUT4 externalization into the cellular membrane to absorb glucose. Chylomicrons or VLDL transport triacylglycerols to adipose tissue depots. During fasting, by the action of glucagon, enzymes are released that will degrade tri-, di- and mono-glycerols to release fatty acids. Adipose tissue releases pro and anti-inflammatory cytokines, as well as leptin and adiponectin that regulate appetite and satiety. AMPK is activated in response to a decrease in the cell's energy and helps it to maintain its energetic balance. In the adipocyte, it promotes the degradation of triacylglycerols releasing fatty acids to be used as an energy source. More studies are needed to learn more about the function of adipose tissue as a regulator of the metabolism and not only as an energy storage.

Bitter gourd extract improves glucose homeostasis and lipid profile via enhancing insulin signaling in the liver and skeletal muscles of diabetic rats

Objective: To investigate the modulatory effects of bitter gourd extract on the insulin signaling pathway in the liver and skeletal muscle tissues of diabetic rats. Methods: The ethanolic extract of bitter gourd was prepared and its contents of total polyphenols and flavonoids were assayed. A neonatal streptozotocin-induced diabetic rat model was established and the diabetic rats were assigned into different groups and were treated with different doses of bitter gourd extract (100, 200, 400, or 600 mg/kg) or with glibenclamide (0.1 mg/kg) for 30 d. Fasting blood glucose, insulin, and lipid profile were evaluated and the insulin signaling pathway in the liver and skeletal muscle of rats was investigated. The correlations between homeostasis model assessment (HOMA) and the components of insulin signaling pathway were also evaluated. Results: Different doses of bitter gourd extract significantly ameliorated fasting blood glucose level and HOMA index for insulin resistance. Moreover, bitter gourd extract increased serum insulin and improved disrupted serum lipid profile. The levels of insulin receptor substrate-1 (IRS-1), p-insulin receptor β (p-IR-β), protein kinase C (PKC), GLUT2, and GLUT4 were improved by treatment with bitter gourd extract. The best results were obtained with 400 mg/kg dose of the extract, the effect of which was equivalent to that of glibenclamide. HOMA in the bitter gourd treated rats was negatively correlated with p-IR-β, IRS-1 and PKC in hepatic and skeletal muscle. HOMA was also negatively correlated with skeletal muscle GLUT4. Conclusions: Bitter gourd extract improves glucose homeostasis and lipid profile in diabetic rats via enhancement of insulin secretion and sensitivity. Therefore, bitter gourd can be used as a potential pharmacological agent for the treatment of type 2 diabetes mellitus.

Effects of Purple frutescens Leaves Polysaccharides on Oxidative Stress and PI 3K/AKT/GLUT4 Signaling Pathway of Pancreatic Tissues in Diabetes Mellitus Model Mice / 中国药房

OBJECTIVE：To study the effects of Purple frute scens leaves polysaccharides （PPLPs）on oxidative stress and PI3K/AKT/GLUT4 signaling pathway of pancreatic tissues in diabetes mellitus （DM）model mice. METHODS ：Totally 60 mice were given intraperitoneal injection of STZ （60 mg/kg）to induce DM model. The 40 successful modeling mice were randomly divided into model group ，metformin group （positive control ，200 mg/kg），PPLPs high-dose and low-dose groups （400，200 mg/kg），with 10 mice in each group. Another 10 healthy mice were selected as the normal group （normal saline ）. They were given relevant medicine intragastrically ，once a day ，for consecutive 28 days. During the experiment ，general information and body weight of mice were observed ；oral glucose tolerance （OGTT）test（determining FBG at 0，30，60，120 min after giving 40％ glucose solution ）was conducted. After last medication ，the changes of related blood glucose indexes （FBG，FINS，ISI，IRI）， blood lipid indexes （HDL-C，LDL-C，TC，TG）and oxidant stress indexes （MDA content and the activities of SOD ，CAT， GSH-Px）as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were determined. RESULTS ：During the experiment ，compared with normal group ，the mice were slow in action ，the feed consumption and water consumption increased，and body weight significantly increased in model group （P＜0.05）. 0，30，60，120 min after giving glucose ，the FBG content of mice were all increased significantly （P＜0.05）. After last medication ，the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all decreased significantly （P＜0.05）；the contents of FBG and LDL-C ，TC and TG in serum as well as IRI ， 疗。E-mail：sunguangping83@163.com MDA content in pancreatic tissue were all increased significantly（P＜0.05）. Compared with model group ，the general condition and OGTT of mice in each administration group was improved；the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all increased significantly （P＜0.05）；the contents of FBG，LDL-C，TC and TG in serum as well as IRI ，MDA content of pancreatic tissue were decreased significantly （P＜0.05）. CONCLUSIONS：PPLPs has anti-diabetic effects ，which are related to reducting oxidative stress level and promoting the activation of PI 3K/AKT/GLUT4 signaling pathway.

Regulation mechanism of Compound Yihe Tea on improving insulin resistance in obesity mice / 中国药科大学学报

@#The aim of this study was to investigate the effect of Compound Yihe Tea on improving insulin resistance in obesity mice. Thirty-two male C57BL/6J mice were randomly divided into 4 groups: the normal fat diet group(NFD group), high fat diet group(HFD group), Compound Yihe Tea low dosage group［20 mg/(kg ·d), YH-L group］ and high dosage group［40 mg/(kg ·d), YH-H group］. NFD group was given standard feed, and the remaining mice were administered with high fat diet. After 6 weeks, YH-H and YH-L groups were given Compound Yihe Tea for 6 weeks. Blood glucose was measured at week 11 and serum levels of total cholesterol(TC), serum triglyceride(TG), low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured at week 12. Liver tissues were prepared for oil red O and HE staining. Immunohistochemical analysis was used to test the protein expression of GLUT4 in liver. Protein expressions of PI3K, Akt and GLUT4 in epididymis white adipose tissue(WAT)were tested by Western blot. The results showed that Compound Yihe Tea could effectively reduce body weights and the serum levels of TC, TG and LDL-C. Furthermore Compound Yihe Tea could improve the histopathological changes of liver, up-regulate the protein expression of PI3K, Akt and GLUT4 in epididymis WAT and the protein expression of GLUT4 in liver. Compound Yihe Tea can reduce the fat accumulation in liver tissue, improve the indexes of blood glucose and lipid levels, and improve insulin resistance via PI3K-AKT-GLUT4 pathway.

Antidiabetic activity of Callicarpa nudiflora extract in type 2 diabetic rats via activation of the AMPK-ACC pathway

Objective: To evaluate the antidiabetic effect of Callicarpa nudiflora extract in streptozotocin-induced diabetic rats. Methods: The chemical constituents in Callicarpa nudiflora extract were identified by UPLC-Q-TOF-MS. Callicarpa nudiflora extract (0.15 and 0.3 g/kg) was orally administered to streptozotocin-induced diabetic rats for 42 d. The effects of Callicarpa nudiflora extract on body weight, blood glucose, serum insulin, total cholesterol, triglyceride, LDL-C and HDL-C were investigated, and its effect on liver and pancreatic pathology was assessed by histopathological analysis. Moreover, the expression levels of adenosine 5'-monophosphate-activated protein kinase (AMPK), glucose transporter type 4 (GLUT4), phospho-AMPK/AMPK, and p-acetyl-coA carboxylase (P-ACC)/ACC in the skeletal muscles and liver were determined by reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Results: A total of 34 compounds, including 8 iridoids, 14 phenylpropanoids, and 12 flavonoids, were identified from Callicarpa nudiflora extract. Callicarpa nudiflora extract significantly reduced blood glucose and significantly restored all other biochemical parameters to near normal levels, including serum insulin, total cholesterol, triglyceride, LDL-C, and HDL-C. Callicarpa nudiflora extract improved insulin resistance and reversed the damage in the liver and pancreas caused by diabetes. Furthermore, Callicarpa nudiflora extract increased the expression levels of phospho-AMPK, GLUT4, P-ACC, and insulin receptor substrate-1 and decreased the expression level of PPAR毭 in diabetic rats.Conclusions: Callicarpa nudiflora extract improved oral glucose tolerance, lipid metabolism, insulin resistance, and reversed the diabetes-related damage in the liver and pancreas by activating the AMPK-ACC pathway.

Antidiabetic effect of combination of fractionated-extracts of Andrographis paniculata and Centella asiatica: In vitro study

Objective: To examine the effect of combination of Andrographis paniculata herb fraction (AHF) and Centella asiatica herb fraction (CHF) on PPARγ and GLUT4 mRNA expressions in 3T3-L1 adipocyte, and its effect on insulin-stimulated glucose uptake. Methods: 3T3-L1 adipocyte cells were used to investigate gene expression of PPARγ and GLUT4 proteins by reverse transcription-polymerase chain reaction method. The adipocyte cells were differentiated by using insulin, dexamethasone and 3-isobutyl-1-methylxanthine from 3T3-L1 cells. Pioglitazone, AHF, CHF and the combination of both herbs were evaluated on glucose uptake activity, PPARγ and GLUT4 mRNA expressions in 3T3-L1 adipocyte. Results: The results showed that combination of AHF at 30 μg/mL and CHF at 10 μg/mL could enhance insulin-stimulated glucose uptake. The combination also increased PPARγ and GLUT4 mRNA expressions significantly in comparison to those of negative control (DMSO). These effects were equal in comparison to those of pioglitazone (0.02 μM) and its single extracts. Conclusions: The combination of AHF and CHF can increase glucose uptake and insulin sensitivity through up-regulation of PPARγ and GLUT4 mRNA expressions in 3T3-L1 adipocyte.

Antidiabetic effect of combination of fractionated-extracts of Andrographis paniculata and Centella asiatica: In vitro study

Objective: To examine the effect of combination of Andrographis paniculata herb fraction (AHF) and Centella asiatica herb fraction (CHF) on PPARγ and GLUT4 mRNA expressions in 3T3-L1 adipocyte, and its effect on insulin-stimulated glucose uptake. Methods: 3T3-L1 adipocyte cells were used to investigate gene expression of PPAR γ and GLUT4 proteins by reverse transcription-polymerase chain reaction method. The adipocyte cells were differentiated by using insulin, dexamethasone and 3-isobutyl-1-methylxanthine from 3T3-L1 cells. Pioglitazone, AHF, CHF and the combination of both herbs were evaluated on glucose uptake activity, PPARγ and GLUT4 mRNA expressions in 3T3-L1 adipocyte. Results: The results showed that combination of AHF at 30 μg/mL and CHF at 10 μg/mL could enhance insulin-stimulated glucose uptake. The combination also increased PPARγ and GLUT4 mRNA expressions significantly in comparison to those of negative control (DMSO). These effects were equal in comparison to those of pioglitazone (0.02 μM) and its single extracts. Conclusions: The combination of AHF and CHF can increase glucose uptake and insulin sensitivity through up-regulation of PPARγ and GLUT4 mRNA expressions in 3T3-L1 adipocyte.

Effects of extract from fermented buckwheat flower and leaf(EFBFL)on myocardial injury in type 2 diabetic db/db mice / 中国药理学通报

Aim To discuss the effectsof extract from fermented buckwheat flower and leaf(EFBFL) on myocardial injury in spontaneously obese type Ⅱ diabetic db/db mice and its mechanism.Methods 9-week-old male db/db mice were randomly divided into high level EFBFL dose group(EFBFL-H, 0.1 g·kg-1), low level EFBFL dose group(EFBFL-L, 0.05 g·kg-1),metformin hydrochloridecontrol group, model control group, and normal control group, with 10 mice in each group.All groups were treated with 8 wks of drugs by gastric perfusion.The random blood glucose(RBG) was tested respectively at the end of 2nd, 4th, 6th, and 8th wk.Finally, the levels of creatine kinase(CK) creatine kinase MB(CK-MB), andadvanced glycosylation endproducts(AGEs) were detected after 8 wks.The morphological changes of myocardium were observed under light microscope by HE staining, and the ultrastructure of myocardium was observed under electron microscope.Immunohistochemical method and Western blot were used to detect myocardial tissue glucose transporter-4(Glut-4).Results EFBFLcould repress patho-proceeding of myocardial fibrosis efficiently, and significantly decrease the level of blood glucose, CK,CK-MB, and AGEs in db/db mice.Meanwhile, it could increase the expression of Glut-4 in myocardial tissues of mice.Conclusions EFBFL can prevent myocardial injury in spontaneously obese type Ⅱ diabetic db/db mice.The possible mechanism may be related to lowering the level of blood glucose and serum AGEs and up-regulating Glut4of cardiac muscle.

Effects of Ji Tang Zhi on glucose metabolism and related protein expression in insulin resistance HepG 2 cell line / 药物评价研究

Objective To evaluate the effect of Ji Tang Zhi on glucose metabolism in insulin resistance (IR) HepG 2 cell line,and to explore the related mechanism.Methods The HepG2 cells were incubated in culture medium addition of 10-7 mol/L insulin for 24 h to establish the IR cell model.Effect of Ji Tang Zhi on rate of glucose absorption in HepG2 cell was detected by the method of glucose oxidase-peroxidase (GOD-POD).We performed an MTT assay to determine cytotoxicity effects of Ji Tang Zhi on HepG2 cell line.The expression of p-IRS-1 Ser307,PI3K and GLUT-4 were detected by Western blotting.Results Incubated with 10-7 mol/L insulin for 24 h,the insulin resistance cell model had been built.Compared with model group,the rate of glucose absorption of cell treated with JTZ (30 ～ 120 μg/mL) was significantly improved.According to model cells,the expression of GLUT-4 and PI3K decreased significantly compared to control cells.While the expression of p-IRS-1 Ser 307 was inhibited and GLUT-4 and PI3K expression were increased in IR cells after treated with JTZ (30 ～ 120 μtg/mL).Conclusion JTZ exert beneficial effects on hyperglycosemia in IR cell line possibly through regulating the levels of GLUT-4,p-IRS-1 Ser307 and PI3K in HepG2 cell.

Effects of orientin on insulin resistance in 3T3-L1 adipocytes and its mechanism / 中国药理学通报

Aim To investigate the effect of orientin on proliferation and differentiation of 3T3-L1 pre-adipocytes and on insulin resistance(IR) in 3T3-L1 adipocytes and the possible mechanisms.Methods MTT assay and oil red O staining were applied to investigate the proliferation and the differentiation of 3T3-L1 pre-adipocytes, respectively.The intracellular triglyceride(TG) contents were detected by enzymatic analysis.IR model was induced with dexamethasone.A fluorescent glucose analogue, 2-NBDG, was used to measure the rate of glucose uptake.Western blot was used to detect the protein level of GLUT4 and phosphorylation of AMPK and ACC.The GLUT4 translocation was measured by fluorescent-immunohistochemistry.Results Orientin decreased the formation of lipid droplets and intracellular TG contents(P<0.01) in a concentration-dependent manner(P<0.05), but it had no obvious effects on the cell vitality.Under the IR state, orientin significantly increased 3T3-L1 adipocytes glucose uptake(P<0.05).Meanwhile, orientin up-regulated the protein expression of p-AMPK, p-ACC, and enhanced GLUT4 translocation and its expression.Conclusion Orientin can effectively inhibit the differentiation of 3T3-L1 pre-adipocytes and increase insulin sensitivity due to the activation of AMPK/GLUT4 signal pathway.

2-Deoxyglucose improves sensitivity of leukemia drug-resistant K562/ADM cells to adriamycin by blocking aerobic glycolysis / 中国药理学通报

Aim To investigate the effect of 2-deoxy-D-glucose(2-DG)on the sensitivity of leukemia multi-drug resistant K562/ADMcells to adriamycin by inhib-iting glycolytic pathway as well as its molecular mecha-nisms.Methods The leukemia drug-resistant K562/ADM cells and parental K562 cells were used as the target cell models.The cell proliferating activity was assessed with an MTT colorimetric assay,and the gly-colysis including glucose consumption,lactate export, and hexokinase activity was determined by glucose, lactic acid and hexokinase (HK)testing kits.The ex-pression and phosphorylation of mammalian target of rapamycin(mTOR)and glucose transporter-4 (GLUT-4)expression were analyzed by western blot.Results K562/ADM drug-resistant cells possessed higher HK activity,GLUT-4 expression level and aerobic glycolic ability than K562 sensitive cells. 2-DG treatment markedly inhibited HK activity,glucose consumption, and lactate export both in K562 cells and K562/ADM cells,and suppressed the proliferation of the two cells in a time-and concentration-dependent manner.Low concentration of 2-DG or adriamycin could increase the expression and phosphorylation of mTOR.However, the co-administration of 2-DG and adriamycin markedly counteracted adriamycin-mediated enhancement of mTOR expression and phosphorylation and down-regu-lated GLUT-4 expression in K562/ADM cells,and 2-DG dramatically improved the sensitivity of K562/ADM cells to cytotoxicity.Conclusion 2-DG inhibits the proliferation of drug-resistant K562/ADM cells and en-hances the sensitivity to adriamycin by blocking aerobic glycolysis pathway through inhibiting hexokinase activi-ty,counteracting adriamycin-stimulated increased ex-pression and phosphorylation of mTOR and downregu-lating GLUT-4 expression.

Study on in vitro hypoglycemic effect and mechanism of Polygonum capitatum / 中草药

Objective: To investigate the hypoglycemic targets of Polygonum capitatum. Methods: Human liver cancer HepG2 cells were adopted to detect the supernatant culture medium glucose content, and the effect on PPAR-α and GLUT4 gene expression was investigated by qRT-PCR after treatment of P. capitatum extracts (PCB). INS-1 cells similar to islet β cells, divided into drug protection group and repair group, were adopted to determine the cell proliferation activity by MTT; The intracellular SOD and MDA levels were measured by biochemical method; The Cyt C and Caspase-3 protein expression levels were detected by Western blotting. Adopting maltose as substrate of α-glycosidase enzyme inhibition model, the inhibitory efficiency of PCB on glycosidic enzyme was determined. Results: PCB group significantly promoted the absorption of HepG2 cells to supernatant glucose and increased the expression of PPAR-α and GLUT4 genes significantly. Aim at protection and repair of INS-1 cells, PCB group significantly increased cell vitality and SOD level, reduced MDA level compared with model group, and at the same time significantly reduced Cyt C and Caspase-3 protein expression levels. PCB had inhibitory activity to α-glycosidase enzymes, with IC50 of 11.53 mg/mL. Conclusion: PCB could significantly increase the PPAR-α and GLUT4 genes expression to promote the absorption of HepG2 cells to supernatant glucose by blocking the Cyt C-Caspase-3 pathways to reduce apoptosis of islet cells which were damaged by STZ and by raising SOD and declining MDA to improve INS-1 cell oxidative stress; What’s more it has inhibitory activity to α-glycosidase enzymes.

Effect of water extract from Jiangtang Decoction on PI3K/Akt signal pathway of skeletal muscle metabolism in KK-Ay diabetic mice / 药物评价研究

Objective To explore the effects of water extract from Jiangtang Decoction (WEJTD) on PI3K/Akt signal pathway of skeletal muscle metabolism in KK-Ay diabetic mice.Methods Totally 50 KK-Ay mice were randomly divided into five groups:model group,metformin (positive drug,250 mg/kg) group,WEJTD low,medium,and high dose (2,4,and 8 g/kg) group,with 10 C57BL/6J mice as normal group.The relative drugs were ig administered once a day for 12 weeks,and mice in control group and model group were perfused with distilled water of equal volume.After 12 weeks' oral administration,mice were executed to separate serum,serum insulin level was detected by ELISA kit method;RNA was extracted from muscle tissue by Trizol,and real-time PCR were used to detect the level of PI3K,Akt,GLUT-4,GSK-3β,GS and IRS-1 mRNA.Results WEJTD can down-regulate concentration of insulin in serum and GSK-3β mRNA in skeletal muscle (P ＜ 0.05 and 0.001),and down-regulate mRNA of PI3K,Akt,IRS-1,GLUT-4,and GS in skeletal muscle (P ＜ 0.05,0.01,and 0.001).Conclusion WEJTD decreased glycogen deposition and stimulated glucose transport in skeletal muscle through upregulation of PI3K/Akt signaling pathway.

Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise

Abstract Glucose uptake is an important phenomenon for cell homeostasis and for organism health. Under resting conditions, skeletal muscle is dependent on insulin to promote glucose uptake.Insulin, after binding to its membrane receptor, triggers a cascade of intracellular reactions culminating in activation of the glucose transporter 4, GLUT4, among other outcomes.This transporter migrates to the plasma membrane and assists in glucose internalization.However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium actto regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulinlevels.Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.(AU)

Effects of Kaempferol on the Skeletal Muscle of KKAy Mice via PI3K-AKT-GLUT4 Signaling / 世界科学技术-中医药现代化

This study aimed to investigate the effects of kaempferol on the skeletal muscle of KKAy mice via PI3K-AKT-GLUT4 signaling.Spontaneous type 2 diabetic KKAy mice were made up for the model group.After 6-week treatment of kaempferol by intragastric administration,key targets of PI3K-AKT-GLUT4 signaling were detected using biochemical and immunohistochemical technique,and western blot.It was found that the body weight,fast blood glucose and random blood glucose were decreased after kaempferol administration.ITT results show that blood glucose at 30 min after injecting insulin and the area under the curve drop were reduced in the kaempferol group,and so was the insulin resistance index in the kaempferol group.In addition,the mRNA expressions of PI3K,AKT and GLUT4 in the kaempferol group increased significantly,while the protein levels of AKT and GLUT4 were up-regulated by kaempferol administration.It was concluded that kaempferol can significantly regulate the blood glucose,body weight and insulin resistance in mice through activating the PI3K-AKT-GLUT4 signaling.

Effect of Sanhuang Decoction on glucose and lipid metabolism in 3 T3-L1 adipocytes / 中国药理学通报

Aim ToobservetheeffectofSanHuang Decoction (SHD )on glucose and lipid metabolism in insulin resistance(IR)3T3-L1 adipocytes.Methods TheIRmodelof3T3-L1adipocyteswasinducedby high glucose and hyperinsulinism cultivation(also con-taining dexamethasone ).The adipocytes were treated with rosiglitazone(Ros)and different concentrations of SHD(2. 5,5,10,20,40 g·L-1 )for 24 h.The content of glucose disappeared from the culture medium was determined as glucose consumption of the cells. The transport of glucose was observed by 2-deoxidation-[3 H]-glucose uptake method.The efflux of nonesteri-fied fatty acids(NEFA)from adipocytes was observed by the concentration of NEFA in the culture medium. The mRNA expression of glucose transporter-4 (GLUT-4)was measured by real-time polymerase chain reac-tion (real-time PCR).The protein expression of GLUT-4wasdetectedbyWesternblot.Results Compared with the Con group,SHD(5,10,20,40 g·L-1 ) could significantly induce the glucose consumption and transportion(P0.05).Conclusion SHDcanin-crease insulin sensitivity by increasing glucose trans-portation and consumption in the 3T3-L1 adipocytes as well as decreasing the NEFA efflux from the cells.

Effects of dietary intake of butyrate on GLUT-4 protein content in rat skeletal muscle / 体力科学

Butyrate is a short-chain fatty acid produced during fermentation of fibers and other substrates in the gastrointestinal tract. A recent study has shown that elevation of butyrate availability by dietary supplementation exerts favorable effects on glucose metabolism. However, it remains unclear whether butyrate intake affects insulin-sensitive glucose transporter (GLUT-4) protein content in skeletal muscle, which has been shown to be closely related to muscle glucose transport capacity and whole-body insulin sensitivity. The purpose of this study was therefore to examine the effects of dietary intake of butyrate on muscle GLUT-4 protein content and whole-body insulin sensitivity in rats. Seven-week-old male Sprague-Dawley rats were placed on a sodium butyrate diet (SB) or standard chow diet (CON) for 2 wks. Sodium butyrate was incorporated into the standard chow diet at 5 % wt/wt. After the 2-wk dietary intervention, insulin tolerance test (ITT) was performed to evaluate whole-body insulin sensitivity. GLUT-4 protein contents in soleus and epitrochlearis muscles were determined by western blot analysis. There were no significant differences in body weight, food intake and intra-abdominal fat weight between the SB and CON groups. GLUT-4 protein contents in soleus and epitrochlearis muscle were significantly lower in the SB than CON group. The SB group had less reduction in glycemia than did the CON group during ITT. These results suggest that dietary intake of sodium butyrate may decrease muscle GLUT-4 protein content and impair whole-body insulin sensitivity in rats.

Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression

This study aimed to evaluate the effects of exercise training on triglyceride deposition and the expression of musclin and glucose transporter 4 (GLUT4) in a rat model of insulin resistance. Thirty male Sprague-Dawley rats (8 weeks old, weight 160±10 g) were fed a high-fat diet (40% calories from fat) and randomly divided into high-fat control group and swimming intervention group. Rats fed with standard food served as normal control. We found that 8-week swimming intervention significantly decreased body weight (from 516.23±46.27 to 455.43±32.55 g) and visceral fat content (from 39.36±2.50 to 33.02±2.24 g) but increased insulin sensitivity index of the rats fed with a high-fat diet. Moreover, swimming intervention improved serum levels of TG (from 1.40±0.83 to 0.58±0.26 mmol/L) and free fatty acids (from 837.80±164.25 to 556.38±144.77 μEq/L) as well as muscle triglycerides deposition (from 0.55±0.06 to 0.45±0.02 mmol/g) in rats fed a high-fat diet. Compared with rats fed a standard food, musclin expression was significantly elevated, while GLUT4 expression was decreased in the muscles of rats fed a high-fat diet. In sharp contrast, swimming intervention significantly reduced the expression of musclin and increased the expression of GLUT4 in the muscles of rats fed a high-fat diet. In conclusion, increased musclin expression may be associated with insulin resistance in skeletal muscle, and exercise training improves lipid metabolism and insulin sensitivity probably by upregulating GLUT4 and downregulating musclin.

Prophylactic efficacy and possible mechanisms of oligosaccharides based standardized fenugreek seed extract on high-fat diet-induced insulin resistance in C57BL/6 mice.

The present work was aimed to study the efficacy and possible mechanism of oligosaccharides based standardized fenugreek seed extract (SFSE-OS) on high-fat diet (HFD)-induced insulin resistance in male C57BL/6 mice. The effects of 12 weeks of oral administration of SFSE-OS (30, 60 and 100 mg/kg, twice daily) were evaluated on HFD fed mice for anthropomorphic, glycemic, gene expression related and histopathological parameters. Separate groups of mice with vehicle co-administered with HFD and low-fat diet (LFD) were maintained as HFD control and LFD control respectively. Twelve weeks of SFSE-OS (60 and 100 mg/kg, p.o.) administration showed significant prophylactic effects on HFD induced insulin resistance in terms of body weight, plasma glucose and insulin levels, glycated hemoglobin, insulin resistance (IR), area under the curve (AUC) of plasma glucose during oral glucose tolerance and intraperitoneal insulin tolerance. Furthermore, HFDinduced mRNA expression changes in adipose tissue, liver and skeletal muscle were prevented by SFSE-OS coadministration. Histology of sections of the pancreas showed the normal architecture in all groups of mice. SFSE-OS showed promising efficacy in prevention of HFD-induced insulin resistance through modulation of Glut-2, Glut-4, IRS-2 and SREBP-1c expression.

Effects of Huazhuo Granule on Expressions of PI-3K and GLUT4 mRNA in Rats with Type 2 Diabetes / 中国中医药信息杂志

Objective To observe the effects of Huazhuo Granule on expression of phosphatidylinositol-3-kinase (PI-3K) and glucose transporter 4 (GLUT4) in skeletal muscle type 2 diabetes (T2DM) rats;To discuss its effects on activating signal path of PI-3K and GLUT4. Methods High-fat diet combined with low-dose streptozotocin intraperitoneal injection was used to establish T2DM rat models. The rats were randomly divided into blank group, Huazhuo Granule group, rosiglitazone group, and model group. Each treatment group was given relevant medicine for gavage. Model group and blank control group were given normal saline for gavage. The general state, weight, and food ration of rats were observed. After ten-week medicine intervention, 10%chloral hydrate was used for anesthesia to detect the levels of FBG, OGTT (2 h PG), and FINS. RT-PCR was used to detect the expressions of PI-3K and GLUT4 mRNA of rat skeletal muscle in all groups. Results Compared with model group, the levels of FBG, 2 h PG, and FINS decreased (P<0.05);the expressions of PI-3K and GLUT4 mRNA of rat skeletal muscle increased significantly (P<0.05). Conclusion Huazhuo Granule has the effects on increasing insulin sensitivity, which is related to activating insulin signal path of PI-3K and GLUT4 of skeletal muscle tissues.