• Preventive Nutrition and Food Science
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• v.10 no.1
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• pp.52-57
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• 2005

Soy and soy foods are a rich source of isoflavones, which possess several biological activities. The effect of soy isoflavones, genistin and diadzin and their respective aglycones, on glucose uptake in adipocytes isolated from normal or high-fat fed rats was examined. As expected, insulin stimulated glucose uptake in a concentration-dependent manner. However, genistin and daidzin and their aglycones inhibited glucose uptake in a concentration-dependent (25-100μM) manner. In a time-course response, the aglycones significantly inhibited glucose uptake throughout 3 hr (after 30, 60, 120, 180 min), whereas the glycones only significantly inhibited the glucose uptake after 120 min and 180 min in the isolated rat adipocytes. Thus, the glucosides of genistein and daidzein, i.e. genistin and daidzin, were much less effective in inhibiting glucose uptake than their aglycones. In addition, genistin and daidzin did not significantly affect the insulin-stimulated glucose uptake, whereas genistein and daidzein did significantly inhibited glucose uptake compared to the vehicle control group by 47.5% and 24.8%, respectively (p < 0.05). The isoflavones also significantly inhibited glucose uptake in adipocytes isolated from rats fed a high-fat diet (50% of total calorie intake) when compared to the vehicle control. Finally, the isoflavones were found to enhance lipolysis in adipocytes isolated from high-fat fed rats, where the glycerol released by the aglycones was also higher than that released by the glycones. The current results showed that the inhibitory effect of daidzein on glucose uptake was very similar to that of genistein. The aglycones were more potent in inhibiting the uptake of glucose and a more potent stimulator of lypolysis than the glycones in adipocytes isolated from high-fat fed rats.

• Preventive Nutrition and Food Science
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• v.16 no.2
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• pp.135-141
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• 2011

Inhibition of intestinal glucose uptake is beneficial in reducing the blood glucose level for diabetes. To search for an effective intestinal glucose uptake inhibitor from natural sources, 70 native edible plants, fruits and vegetables were screened using Caco-2 cells and fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG). A compound that was able to inhibit glucose uptake was isolated from methanol extract of Punica granatum L. and called PG-1a. PG-1a appears to be a phthalic acid-diisononyl ester- like compound (PDE) with molecular weight of 418. The inhibitory effect of PG-1a on intestinal glucose uptake was dose-dependent with 89% inhibition at $100\;{\mu}g$/mL. Furthermore, the intestinal glucose uptake inhibitory effect of PG-1a was 1.2-fold higher than phlorizin, a well known glucose uptake inhibitor. This study suggests that PG-1a could play a role in controlling the dietary glucose absorption, and that PG-1a can effectively improve the diabetic condition, and may be used as an optional therapeutic and preventive agent.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.94-98
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• 2016

The objective of the present study was to elucidate the effect of bisphosphonates, anti-osteoporosis agents, on glucose uptake in retinal capillary endothelial cells under normal and high glucose conditions. The change of glucose uptake by pre-treatment of bisphosphonates at the inner blood-retinal barrier (iBRB) was determined by measuring cellular uptake of $[^3H]3$-O-methyl glucose (3-OMG) using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB cells) under normal and high glucose conditions. $[^3H]3$-OMG uptake was inhibited by simultaneous treatment of unlabeled D-glucose and 3-OMG as well as glucose transport inhibitor, cytochalasin B. On the other hand, simultaneous treatment of alendronate or pamidronate had no significant inhibitory effect on $[^3H]3$-OMG uptake by TR-iBRB cells. Under high glucose condition of TR-iBRB cells, $[^3H]3$-OMG uptake was increased at 48 h. However, $[^3H]3$-OMG uptake was decreased significantly by pre-treatment of alendronate or pamidronate compared with the values for normal and high glucose conditions. Moreover, geranylgeraniol (GGOH), a mevalonate pathway intermediate, increased the uptake of $[^3H]3$-OMG reduced by bisphosphonates pre-treatment. But, pre-treatment of histamine did not show significant inhibition of $[^3H]3$-OMG uptake. The glucose uptake may be down regulated by inhibiting the mevalonate pathway with pre-treatment of bisphosphonates in TR-iBRB cells at high glucose condition.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.1
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• pp.59-62
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• 2014

Glucose uptake plays a pivotal role in maintaining whole body glucose homeostasis in adipocytes and skeletal muscles. In the present study we have shown that Fructus Piperis Longi Extracts (FPLE) can stimulate glucose uptake in OP9 adipocytes. The increasing effects of FPLE on glucose uptake were inhibited by compound C pretreatment, which means that the glucose uptake effects by FPLE were carried out by AMP-activated protein kinase (AMPK) activation. Further studies revealed that FPLE stimulated glucose transport occurs through a mechanism involving extracellular signal-regulated kinase (ERK1/2) activation.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.155-161
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• 2007

Objectives: Evidences suggests that Ginkgo biloba, a widely used traditional medicine, shows a hypoglycemic effect. Thus, we investigatd the effect of G. biloba extract (GB) on glucose uptake in L6 rat skeletal muscle cells. Method : Effect of GB on glucose uptake and phosphatidylinositol (PI) 3-kinase activity were assessed using Glucose uptake assay and PI 3-kinase assay, respectively. Also, AMP-activated protein kinase (AMPK), p38 mitogen activated protein kinase (p38 MAPK) expression were identified by Western blot. Results : Glucose uptake assay revealed that GB increased glucose uptake about 2.5-fold compared to thecontrol. GB stimulated the activity of PI 3-kinase which is a major switch element on the glucose uptake pathway. About a 6.5-fold increase in activity of PI 3-kinase was observed with GB. We then assessed the activity of AMPK, another regulatory molecule on the glucose uptake pathway. The result was that GB increased the phosphorylation level of both AMPK ${\alpha}$l and ${\alpha}$2. The activity of p38 MAPK, a downstream mediator of AMPK, was also increased by CB. Conclusion : These results suggest that GB may stimulate glucose uptake through both PI 3-kinase and AMPK mediated pathways in L6 skeletal muscle cells thereby contributing to glucose homeostasis.

• Journal of Veterinary Science
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• v.22 no.6
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• pp.92.1-92.12
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• 2021

Background: Naringin and its aglycone naringenin are citrus-derived flavonoids with several pharmacological effects. On the other hand, the mechanism for the anti-diabetic effects of naringenin and naringin are controversial and remain to be clarified further. Objective: This study examined the relationship between glucose uptake and AMP-activated protein kinase (AMPK) phosphorylation by naringenin and naringin in high glucose-treated HepG2 cells. Methods: Glucose uptake was measured using the 2-NBDG fluorescent D-glucose analog. The phosphorylation levels of AMPK and GSK3β (Glycogen synthase kinase 3 beta) were observed by Western blotting. Molecular docking analysis was performed to evaluate the binding affinity of naringenin and naringin to the γ-subunit of AMPK. Results: The treatment with naringenin and naringin stimulated glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Both flavonoids increased glucose uptake by promoting the phosphorylation of AMPK at Thr172 and increased the phosphorylation of GSK3β. Molecular docking analysis showed that both naringenin and naringin bind to the γ-subunit of AMPK with high binding affinities. In particular, naringin showed higher binding affinity than the true modulator, AMP with all three CBS domains (CBS1, 3, and 4) in the γ-subunit of AMPK. Therefore, both naringenin and naringin could be positive modulators of AMPK activation, which enhance glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Conclusions: The increased phosphorylation of AMPK at Thr172 by naringenin and naringin might enhance glucose uptake regardless of insulin stimulation in high glucose treated HepG2 cells.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.11
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• pp.1690-1694
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• 2003

The large and rapid changes of glucose utilization in lactating mammary tissue in response to changes in nutritional state must be largely related by external signal of insulin. This also must be related with the quantity and composition of the diet in vivo. To characterize the mode of growth factors and gut regulatory peptides with insulin, in vitro experiment was conducted with HC11 cells. All the growth factor alone and the combinations of growth factors significantly (p<0.05) increased in glucose uptake. Insulin, EGF and IGF-1 exhibited a stimulation of glucose uptake for at least 24 h. Furthermore, the highest (p<0.05) synergistic effect was shown in EGF plus IGF-1 and the second synergistic effect in insulin plus EGF while no synergistic effect was found between insulin and IGF-1. However, the gut regulatory peptides neither potentiated nor inhibited the action of insulin on glucose uptake. Although growth factors did not modulates glucose uptake via increasing the rate of translation of the GLUT1 protein, RT-PCR analysis indicated that the growth factors significantly (p<0.05) increased the expression of GLUT1. The growth factors are therefore shown to be capable of modulating glucose uptake by transcription level with insulin in HC 11 cells.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.195-201
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• 2005

High extracellular glucose concentration was reported to suppress intracellular $Ca^{2+}$ clearing through altered sarcoplasmic reticulum (SR) function. In the present study, we attempted to elucidate the effects of pyruvate and fatty acid on SR function and reveal the mechanistic link with glucose-induced SR dysfunction. For this purpose, SR $Ca^{2+}$-uptake rate was measured in digitonin-permeabilized H9c2 cardiomyocytes cultured in various conditions. Exposure of these cells to 5 mM pyruvate for 2 days induced a significant suppression of SR $Ca^{2+}$-uptake, which was comparable to the effects of high glucose. These effects were accompanied with decreased glucose utilization. However, pyruvate could not further suppress SR $Ca^{2+}$-uptake in cells cultured in high glucose condition. Enhanced entry of pyruvate into mitochondria by dichloroacetate, an activator of pyruvate dehydrogenase complex, also induced suppression of SR $Ca^{2+}$-uptake, indicating that mitochondrial uptake of pyruvate is required in the SR dysfunction induced by pyruvate or glucose. On the other hand, augmentation of fatty acid supply by adding 0.2 to 0.8 mM oleic acid resulted in a dose-dependent suppression of SR $Ca^{2+}$-uptake. However, these effects were attenuated in high glucose-cultured cells, with no significant changes by oleic acid concentrations lower than 0.4 mM. These results demonstrate that (1) increased pyruvate oxidation is the key mechanism in the SR dysfunction observed in high glucose-cultured cardiomyocytes; (2) exogenous fatty acid also suppresses SR $Ca^{2+}$-uptake, presumably through a mechanism shared by glucose.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.257-267
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• 1996

Diabetes mellitus is associated with a wide range of pathophysiologic changes in the kidney. This study was designed to examine the mechanisms by which glucose modulates the expression of polarized membrane transport functions in primary cultured rabbit renal proximal tubule cells. Results are as follows: The rate of 30 minute $Rb^{+}$ uptake was significantly higher($137.76{\pm}5.40%$) in primary renal tubular cell cultures treated with 20 mM glucose than that of 5 mM glucose. Not the level of mRNA for the ${\alpha}$ subunit of Na, K-ATPase but that of ${\beta}$ subunit was elevated in primary cultures treated with high glucose. The initial rate of methyl-${\alpha}$-D-glucopyranoside(${\alpha}$-MG) uptake was significantly lower($71.91{\pm}3.02%$) in monolayers treated with 20 mM glucose than that of 5 mM glucose. There was a tendency of an increase in phlorizin binding site in cells treated with 5 mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. TPA inhibited $Rb^{+}$ uptake by $63.61{\pm}1.94\;and\;45.80{\pm}1.36%$ and ${\alpha}$-MG uptake by $48.54{\pm}3.69\;and\;41.87{\pm}6.70%$ in the cells treated with 5 and 20 mM glucose, respectively. Also TPA inhibited mRNA expression of Na/glucose cotransporter in cells grown in 5mM glucose medium. cAMP significantly stimulated ${\alpha}$-MG uptake by $114.65{\pm}5.70%$ in cells treated with 5mM glucose, while it did not affect ${\alpha}$-MG uptake in cell treated with 20 mM glucose. However, cAMP inhibited $Rb^{+}$ uptake by $76.69{\pm}4.16\;and\;66.87{\pm}2.41%$ in cells treated with 5 and 20 mM glucose, respectively. In conclusion, the activity of the renal proximal tubular Na,K-ATPase is elevated in high glucose concentration. In contrast, the activity of the Na/glucose cotransport system is inhibited. High glucose may in part affect the activity of the Na,K-ATPase and the Na/glucose cotransport system by controlling the protein kinase C and/or A signal transduction pathway in primary cultured renal proximal tubule cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.195-199
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• 2014

Although the Herba Cirsii is known to posses beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. In the present study we have shown that Herba Cirsii Extract (HCE) can stimulate glucose uptake in OP9 adipocytes. Unlike insulin, HCE did not stimulate the Ser473 phosphorylation and activation of Akt. The increasing effects of HCE on glucose uptake were inhibited by PD680509 and compound C pretreatment, which means that the glucose uptake effects by HCE were carried out by extracelluar signal-regulated kinase1/2(ERK1/2) and AMP-activated protein kinase (AMPK) activation. Further studies revealed that HCE stimulated glucose transport occurs through a mechanism involving ERK1/2 activation and AMPK activation.