• Title/Summary/Keyword: GLUT-2

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Morin alleviates fructose-induced metabolic syndrome in rats via ameliorating oxidative stress, inflammatory and fibrotic markers

  • Heeba, Gehan Hussein;Rabie, Esraa Mohamed;Abuzeid, Mekky Mohamed;Bekhit, Amany Abdelrehim;Khalifa, Mohamed Montaser
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.3
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    • pp.177-187
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    • 2021
  • Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

The effects of Allomyrina dichotoma larval extract on palmitate-induced insulin resistance in skeletal muscle cells (장수풍뎅이 유충 추출물이 고지방산 처리 골격근세포의 인슐린 저항성에 미치는 영향)

  • Kim, Kyong;Sim, Mi-Seong;Kwak, Min-Kyu;Jang, Se-Eun;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.55 no.4
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    • pp.462-475
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    • 2022
  • Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

Effects of Palmijihwangtang (PMT) and Exercise on Glucose Metabolism in Myocardium Cell Membrane and Pancreas $\beta$-Cell of Zucker Diabetic Fatty Rats

  • Lee Myeong-Jong
    • The Journal of Korean Medicine
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    • v.25 no.4
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    • pp.200-208
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    • 2004
  • Objective: Non-insulin Dependent Diabetes Mellitus (NIDDM) is characterized by insulin resistance, which affects the glucose transportation inside the cell. The purpose of this study was to find out how Palmijihwangtang (PMT) and exercise influence the glucose transport metabolism in the organ muscles of ZDF (zucker diabetic fatty) rat with insulin resistance. Methods: Using three male normal zucker rats and twelve male obese rats, they were divided into a normal lean group (N=3), obese control group (N=3), obese exercises group (N=3), obese medication group (N=3), obese exercise and medication group (N=3). Treadmill exercise were repeated with 27m/min speed for an hour a day, five days a week, for 8 weeks. And 20β/sub ¢/ of PMT was orally administered twice a day for 8 weeks, after that a period blood sample was exsanguinated by heart perforation and was analyzed. Results: The body weight of the OM and OEM group showed a significant decrease among all the obese groups. The blood insulin level increased significantly of all groups in comparison with the N group. All of the OE, OM and the OEM groups showed a significant decrease of insulin level compared with the OC group; especially the OEM group demonstrated the most among obese groups. Regarding GLUT-4 level, OEM was the unique group showed a significant increase among all the obese groups. The VAMP-2 level in myocardium cell membrane was increased significantly at OC group in comparison with the N group, whereas the OEM group only showed significant decrease of it. In addition, the VAMP-2 level in pancreas β-cell was significantly decreased at all the obese groups in comparison with the N group. Only the OEM group showed significant increase among all the obese groups. Conclusion: Palmijihwangtang (PMT) and exercise could effectively promote the insulin metabolism in pancreas β-cells and activate the glucose transport process in myocardium cell membrane by lowering the insulin resistance of ZDF rats.

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Extracts of Adlay, Barley and Rice Bran have Antioxidant Activity and Modulate Fatty Acid Metabolism in Adipocytes (율무, 보리, 미강 유기용매 추출물의 항산화능과 포도당 및 지방산 대사에 미치는 영향)

  • Park, Tae-Sik;Lee, Su-Yeon;Kim, Hyun-Jin;Kim, Kyung-Tack;Kim, Young-Jun;Jeong, In-Hye;Do, Wan-Nyo;Lee, Hye-Jeong
    • The Korean Journal of Food And Nutrition
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    • v.22 no.3
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    • pp.456-462
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    • 2009
  • Adlay, barley and rice bran were extracted using various concentrations of methanol(10% and 80%) and chloroform : methanol(2 : 1) to examine the biological activities of these raw grains. Extraction with 80% methanol resulted in high Vitamin C Equivalent Antioxidant Capacity(VCEAC), in the order of barley > rice bran > adlay, as determined by DPPH and ABTS assays. In addition, the extracts of adlay and rice bran showed high cellular antioxidant activity in HepG2 cells possibly due to the presence of polyphenol glycosides in these grains. We examined the expression of glucose/fatty acid metabolizing genes in differentiated 3T3-L1 adipocyte cells. Glut1 was downregulated after treatment with rice bran and no changes in the expression of Glut4 was observed. In contrast, genes involved in fatty acid metabolism, CD36 and aP2, were upregulated. Since these physiological changes were matched with peroxisome proliferator activating receptor $\gamma$(PPAR $\gamma$) agonism, we suggest that the extracts from adlay, barley and rice bran may play preventive roles against aging and diabetes via antioxidant activity and increased uptake of fatty acids by adipocytes.

Tenebrio molitor (Mealworm) Extract Improves Insulin Sensitivity and Alleviates Hyperglycemia in C57BL/Ksj-db/db Mice (C57BL/Ksj-db/db 제 2형 당뇨모델을 이용한 갈색거저리 유충(밀웜) 추출물의 인슐린 감수성 및 혈당개선효과)

  • Kim, Seon Young;Park, Jae Eun;Han, Ji Sook
    • Journal of Life Science
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    • v.29 no.5
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    • pp.570-579
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    • 2019
  • Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.

Ishige okamurae reduces blood glucose levels in high-fat diet mice and improves glucose metabolism in the skeletal muscle and pancreas

  • Yang, Hye-Won;Son, Myeongjoo;Choi, Junwon;Oh, Seyeon;Jeon, You-Jin;Byun, Kyunghee;Ryu, Bo Mi
    • Fisheries and Aquatic Sciences
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    • v.23 no.9
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    • pp.24.1-24.9
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    • 2020
  • Brown alga (Ishige okamurae; IO) dietary supplements have been reported to possess anti-diabetic properties. However, the effects of IO supplements have not been evaluated on glucose metabolism in the pancreas and skeletal muscle. C57BL/6 N male mice (age, 7 weeks) were arranged in five groups: a chow diet with 0.9% saline (NFD/saline group), high-fat diet (HFD) with 0.9% saline (HFD/saline group). high-fat diet with 25 mg/kg IO extract (HFD/25/IOE). high-fat diet with 50 mg/kg IO extract (HFD/50/IOE), and high-fat diet with 75 mg/kg IO extract (HFD/75/IOE). After 4 weeks, the plasma, pancreas, and skeletal muscle samples were collected for biochemical analyses. IOE significantly ameliorated glucose tolerance impairment and fasting and 2 h blood glucose level in HFD mice. IOE also stimulated the protein expressions of the glucose transporters (GLUTs) including GLUT2 and GLUT4 and those of their related transcription factors in the pancreases and skeletal muscles of HFD mice, enhanced glucose metabolism, and regulated blood glucose level. Our results suggest Ishige okamurae extract may reduce blood glucose levels by improving glucose metabolism in the pancreas and skeletal muscle in HFD-induced diabetes.

Study of the effect of diet supplemented with powdered Salicornia herbacea L. on glucose transporter and antioxidant capacities in rats

  • Seo, Hyo-Bin;Nam, Ju-Ock;Song, Young-Ju;Kwon, Tae-Dong;Yeo, Yunghi;Ryu, Sungpil
    • Korean Journal of Exercise Nutrition
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    • v.16 no.2
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    • pp.85-92
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    • 2012
  • This study was conducted to examine the possibility of Salicornia herbacea L. powder as a functional food beneficially affecting carbohydrate metabolism and antioxidant capacity. Twenty-four, 6-week old, maleSprague-Dawleyrats were classified into three groups: normal diet control (CON), high-fat diet control (HFC) and high fat diet + Salicornia herbacea L. (SHF). Related feed was provided to each group for 4 weeks. Weight gain rate increased most in the HFC rats, and the concentration of glucose was significantly high in both the HFC and SHF groups, compared to the CON group. The SHF group showed a significantly high expression rate of Glut 4 (21.36%), compared to the CON and HFC groups. The glycogen content in muscle was significantly high in both the HFC and SHF groups, compared to the CON group. There were significant differences in the malondialdehydecontent in muscles between the groups, with the content in the CON and HFC groups being significantly higher than the SHF group. All the groups showed a similar tendency to each other in the liver tissue as well. Concerning the expression of Cu,Zn-super oxide dismutase andglutathione peroxidaseproteins, the SHF group was significantly higher than the CON and HFC groups. Overall, the experiment result above implies a possibility that an intake of Salicornia herbacea L. powder can regulate weight by decreasing the weight gain rate, further suggesting its effectiveness as a functional food before exercise by increasing the energy storage capacity and antioxidant capacity.

Exendin-4 Improves Nonalcoholic Fatty Liver Disease by Regulating Glucose Transporter 4 Expression in ob/ob Mice

  • Kim, Seok;Jung, Jaehoon;Kim, Hwajin;Heo, Rok Won;Yi, Chin-Ok;Lee, Jung Eun;Jeon, Byeong Tak;Kim, Won-Ho;Hahm, Jong Ryeal;Roh, Gu Seob
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.4
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    • pp.333-339
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    • 2014
  • Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.

Anti-Diabetic Effect of Pectinase-Processed Ginseng Radix (GINST) in High Fat Diet-Fed ICR Mice

  • Yuan, Hai Dan;Quan, Hai Yan;Jung, Mi-Song;Kim, Su-Jung;Huang, Bo;Kim, Do-Yeon;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.35 no.3
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    • pp.308-314
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    • 2011
  • In the present study, we investigate anti-diabetic effect of pectinase-processed ginseng radix (GINST) in high fat diet-fed ICR mice. The ICR mice were divided into three groups: regular diet group, high fat diet control group (HFD), and GINSTtreated group. To induce hyperglycemia, mice were fed a high fat diet for 10 weeks, and mice were administered with 300 mg/kg of GINST once a day for 5 weeks. Oral glucose tolerance test revealed that GINST improved glucose tolerance after glucose challenge. Compared to the HFD control group, fasting blood glucose and insulin levels were decreased by 57.8% (p<0.05) and 30.9% (p<0.01) in GINST-treated group, respectively. With decreased plasma glucose and insulin levels, the insulin resistance index of the GINST-treated group was reduced by 68.1% (p<0.01) compared to the HFD control group. Pancreas of GINST-treated mice preserved a morphological integrity of islets and consequently having more insulin contents. In addition, GINST up-regulated the levels of phosphorylated AMP-activated protein kinase (AMPK) and its target molecule, glucose transporter 4 (GLUT4) protein expression in the skeletal muscle. Our results suggest that GINST ameliorates a hyperglycemia through activation of AMPK/GLUT4 signaling pathway, and has a therapeutic potential for type 2 diabetes.

Antidiabetic Activity of IH-901 in db/db Mice (db/db 마우스에서 IH-901의 항 당뇨 활성)

  • Choi, Yun-Suk;Han, Gi-Cheol;Han, Eun-Jung;Park, Keum-Joo;Park, Jong-Suk;Sung, Jong-Hwan;Chung, Sung-Hyun
    • YAKHAK HOEJI
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    • v.50 no.6
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    • pp.345-350
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    • 2006
  • The pharmacological properties of ginseng are mainly attributed to ginsenosides, the active constituents that are found in the extracts of different species of ginseng. Lately; the studies on ginsenosides are mainly focused on IH-901, a major intestinal bacterial metabolite of ginsenosides. In this study; we examined the anti-diabetic activity of IH-901 in C57BU61 db/db mice model. IH-901 was administrated orally at a dose of 20 mg/kg for 5 weeks. During the experimental period, body weight and blood glucose levels were measured every week. After 5 weeks, db/db mice were sacrificed and diabetic parameters were analyzed. IH-901 treated group showed a significant decrease in fasting blood glucose levels (from 10.5 mM to 9.4 mM), insulin resistance index (from 163.6 to 100.2) and triglyceride levels (from 115.3 to 70.1) compared to the diabetic control. In Pancreatic islets morphology; IH-901 treated group revealed much less infltrated mononuclear cells, indicating that IH-901 recovered ${\beta}$-cell damage due to hyperglycemia. In addition, IH-901 upregulated expressions of glucose transporter 4 (GLUT4) and PPAR-${\gamma}$ in skeletal muscle and adipose tissue, respectively. Taken together IH-901might be a potential anti-hyperglycemic agent with insulin sensitizing effect.