• Title/Summary/Keyword: Glut

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Identification of Genetic Variations in CBL, SORBS1, CRK, and RHOQ, Key Modulators in the CAP/TC10 Pathway of Insulin Signal Transduction, and Their Association with Type 2 Diabetes Mellitus in the Korean Population

  • Hong, Kyung-Won;Jin, Hyun-Seok;Lim, Ji-Eun;Go, Min-Jin;Lee, Jong-Young;Hwang, Sue-Yun;Park, Hun-Kuk;Oh, Berm-Seok
    • Genomics & Informatics
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    • v.7 no.2
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    • pp.53-56
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    • 2009
  • Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking, and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL, and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.

The effects of Atractylodes japonica Koidz. on type 2 diabetic rats (창출이 제 2형 당뇨병 흰쥐에 미치는 영향)

  • Lee, Dae Hoon;Han, Jae Min;Yang, Woong Mo
    • The Journal of Korean Medicine
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    • v.36 no.1
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    • pp.75-85
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    • 2015
  • Objectives: Type 2 diabetes mellitus is a metabolic disease characterized by insulin resistance and high blood glucose level from progressive insulin secretory defect. The rhizome of Atractylodes japonica Koidz. (AJ) has been used for treatment of retention of water in oriental medicine. The aim of this study is to examine the effects of AJ on type 2 diabetes rats. Methods: Type 2 diabetes was induced by 60% high fat diet and low dose streptozotocin. Rats were divided into 4 groups (n = 6); Nor (normal control group), Con (diabetic group treated with vehicle), Met (diabetic group treated with 200 mg/kg metformin) and AJ (diabetic group treated with 100 mg/kg AJ). The body weights and food intakes were measured during the treatment period. After 4 weeks treatment, blood glucose level, HOMA-IR, and protein expressions of IRS-1, p-IRS-1, PPAR-${\gamma}$, and GLUT4 were measured, and histopathological examination of beta cell was performed. Results: Compared with the control group, blood glucose level and HOMA-IR were reduced in rats treated with AJ. Impaired beta cells in pancreas of rats were recovered and phosphorylation of IRS-1 was increased in rats treated with AJ. And also, protein expressions of PPAR-${\gamma}$ and GLUT4 were increased by treatment of AJ. Conclusions: The results suggest that Atractylodes japonica Koidz. may have anti-diabetic effect on type 2 diabetic rats through regulation of blood glucose level and insulin resistance. Therefore Atractylodes japonica Koidz. may have positive effects on patients with type 2 diabetes.

Tazarotene-Induced Gene 1 Interacts with DNAJC8 and Regulates Glycolysis in Cervical Cancer Cells

  • Wang, Chun-Hua;Shyu, Rong-Yaun;Wu, Chang-Chieh;Chen, Mao-Liang;Lee, Ming-Cheng;Lin, Yi-Yin;Wang, Lu-Kai;Jiang, Shun-Yuan;Tsai, Fu-Ming
    • Molecules and Cells
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    • v.41 no.6
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    • pp.562-574
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    • 2018
  • The tazarotene-induced gene 1 (TIG1) protein is a retinoidinducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.

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.

Saengmaeksan, a traditional herbal formulation consisting of Panax ginseng, ameliorates hyperuricemia by inhibiting xanthine oxidase activity and enhancing urate excretion in rats

  • Sung, Yoon-Young;Yuk, Heung Joo;Kim, Dong-Seon
    • Journal of Ginseng Research
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    • v.45 no.5
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    • pp.565-574
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    • 2021
  • Background: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, Panax ginseng, Schisandra chinensis, and Liriope platyphylla. SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown. Methods: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on in vitro XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC). Results: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1b levels in both the serum and kidneys. SMS-E inhibited both in vitro XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W. Conclusion: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

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 steam heat processing of Helianthus tuberosi Rhizoma on Blood glucose lowering (국우(菊芋) 증자가 혈당강하작용에 미치는 영향)

  • Kim, Jin-Woo;Ha, Mi-Ae;Shin, Yong-Wook
    • The Korea Journal of Herbology
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    • v.32 no.5
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    • pp.39-46
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    • 2017
  • Objective : This study was designed to evaluate the hypoglycemic effects of Helianthus tuberosi Rhizoma extracts and its optimum Heat processing conditions Methods : We investigated the Salivary ${\alpha}$-amylase, pancreas ${\alpha}$-amylase and ${\alpha}$-glucosidase inhibitory activities of extracts from Steam Heated Helianthus tuberosi Rhizoma Ext. The inhibitory activities of a 50% EtOH extract of Steam Heated Helianthus tuberosi Rhizoma Ext against ${\alpha}$-glucosidases were evaluated in this study. Inhibiting these enzymes involved in the absorption of disaccharides significantly decreases the postprandial increase in blood glucose level after a mixed carbohydrate diet. Furthermore, the postprandial blood glucose lowering effect of Steam Heated Helianthus tuberosi Rhizoma Ext. was compared to a known type 2 diabetes drug(Acarbose(R)) in a mice model. Steam Heated Helianthus tuberosus L. Ext significantly reduced the blood glucose increase after glucose loading. Results : The results were confirmed by real-time PCR that after treated with Streptozotocin in L6 cells, induced expression of GLUT4, after the steamed Helianthus tuberosus L. Ext. treated, observed its expression was increased. Steam Heated Helianthus tuberosus L Ext treated 4 hours in L6 cells, cytotoxicity was measured in MTT assay. Its toxicity were 5.7%, 9% and 11.3% at the treatment concentration $12.5{\mu}g/m{\ell}$, $25{\mu}g/m{\ell}$, the $50{\mu}g/m{\ell}$ respectively. Conclusions : Overall, the results of this study indicate that Hypoglycemic effect of Helianthus tuberosi Rhizoma caused by the Steam heat treatment, the optimum Heat processing condition is steamming at $121^{\circ}C$ for 30 min, and it will provide the basis for developing a useful dietary supplement for controlling postprandial hyperglycemia.

Exploring the quality standard of Phellinus spp through β-glucan content and sensory evaluation (β-glucan 함량과 관능검사를 통한 상황버섯 품질기준 모색)

  • Shin, Yong-Wook
    • The Korea Journal of Herbology
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    • v.32 no.4
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    • pp.47-52
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    • 2017
  • Objective : Phellinus spp. mushroom is an object of interest because it has excellent anticancer effect. Owing to the similalarities in the morphology, Phellinus linteus and Phellinus baumii are often used as same Sang Hwang Mushroom in the Korean market.. The quality control for mushrooms is needed because there are many differences in the efficacy according to cultivation method and cultivation area. Therefore, a reliable authentication method of these herbal medicine is necessary to compare and measure the amount of beta-glucan which is known to have a hypoglycemic effect, from the mushrooms collected in various regions Methods : 7 samples of medicinal mushrooms supplying phellinus spp. were collected in Korea, China and Cambodia. We investigated the hardness, colors, extract ratio, ${\alpha}-amylase$ and ${\alpha}-glucosidase$ inhibitory activities, glucose transporter 4 (GLUT-4) expressions of water extracts from Phellinus spp and also MTT assay were examined for cell toxicity. Results : The results revealed that Phellinus spp.water Ext.inhibited ${\alpha}-glucosidase$ activity. glucose transporter 4 (GLUT-4), the key insulin signaling pathway transcription factor, was remarkably increased by the Phellinus baumii water extract Conclusions : These results suggest that The more yellowish the mushroom is, the lower the hardness, the more the content of ${\beta}-glucan$ is proportional. Because the more ${\beta}-glucan$, the greater the effect of hypoglycemia. compared to the hypoglycemic effect, Phellinus Baumii grown at hanging on selves for 7 month in the green house is the best.

Ginsenoside F2 enhances glucose metabolism by modulating insulin signal transduction in human hepatocarcinoma cells

  • Shengqiang Han ;Long You ;Yeye Hu ;Shuai Wei ;Tingwu Liu ;Jae Youl Cho ;Weicheng Hu
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.420-428
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    • 2023
  • Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

Anti-Obesity Potential through Regulation of Carbohydrate Uptake and Gene Expression in Intestinal Epithelial Cells by the Probiotic Lactiplantibacillus plantarum MGEL20154 from Fermented Food

  • So Young Park;Jin Won Choi;Dong Nyoung Oh;Eun Ji Lee;Dong Pil Kim;Sun Jay Yoon;Won Je Jang;Sang Jun Han;Seungjun Lee;Jong Min Lee
    • Journal of Microbiology and Biotechnology
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    • v.33 no.5
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    • pp.621-633
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    • 2023
  • We investigated the probiotic characteristics and anti-obesity effect of Lactiplantibacillus plantarum MGEL20154, a strain that possesses excellent intestinal adhesion and viability. The in vitro properties, e.g., gastrointestinal (GI) resistance, adhesion, and enzyme activity, demonstrated that MGEL20154 is a potential probiotic candidate. Oral administration of MGEL20154 to diet-induced obese C57BL/6J mice for 8 weeks resulted in a feed efficacy decrease by 44.7% compared to that of the high-fat diet (HFD) group. The reduction rate of weight gain was about 48.5% in the HFD+MGEL20154 group compared to that of the HFD group after 8 weeks, and the epididymal fat pad was also reduced in size by 25.2%. In addition, the upregulation of the zo-1, pparα, and erk2, and downregulation of the nf-κb and glut2 genes in Caco-2 cells by MGEL20154 were observed. Therefore, we propose that the anti-obesity effect of the strain is exerted by inhibiting carbohydrate absorption and regulating gene expression in the intestine.