• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.760-765
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• 1998

Background: Glucose uptake has been found to be increased in cancer cells, and FDG-PET imaging is used for diagnosis of cancer using this phenomenon. However, the exact mechanism of increased glucose uptake in cancer cells has not been clarified. Recent studies demonstrated the presence of glucose transporter(GLUT) mRNA expression in gastrointestinal cancer and head and neck cancer, and suggested that GLUT may be associated with glucose uptake in cancer cells. In lung cancer cells, glucose metabolism is also known to be increased. We evaluated GLUT mRNA expression in human lung cancer cell lines in order to find out the mechanism of increased glucose uptake in lung cancer. Method: Total RNA was isolated from 15 human lung cancer cell lines and immortalized bronchial epithelial cell line(BEAS-2B). After electrophoresis of $20{\mu}g$ total RNA, Northern blot analysis was done using GLUT1 cDNA and GLUT3 cDNA as probes. Results: Thirteen of 14 human lung cancer cell lines expressed GLUT1 mRNA and 10 of 14 human lung cancer cell lines expressed GLUT3 mRNA. Eight human lung cancer cell lines expressed both GLUT mRNAs. BEAS-2B expressed GLUT1 mRNA and did not express detectable GLUT3 mRNA. Conclusion: The increase of glucose metabolism in lung cancer may be associated with GLUT1 and GLUT3 expression.

• YAKHAK HOEJI
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• v.55 no.4
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• pp.301-308
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• 2011

Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

• 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.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.76.1-76.14
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• 2022

Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca²⁺/P⁵⁺ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

• The Korean Journal of Nuclear Medicine
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• v.36 no.2
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• pp.110-120
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• 2002

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied $[^{18}F]$ fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5 - 10.8 mU/mg), while SNU-C5 and monocytes showed lower range of hexokinase activity (4.3 - 6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

• Journal of Life Science
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• v.32 no.10
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• pp.762-770
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• 2022

Hyperglycemia in type 2 diabetes can be alleviated by promoting cellular glucose uptake. Betulinic acid (3β,-3-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic lupane-type triterpenoid compound. Although there have been studies on the antidiabetic activity of betulinic acid, studies on cellular glucose uptake are lacking. We investigated the effects of betulinic acid on glucose uptake and its mechanism of action in 3T3-L1 adipocytes. Betulinic acid significantly stimulated glucose uptake in 3T3-L1 adipocytes by increasing the phosphorylation of the insulin receptor substrate 1-tyrosine (IRS-1tyr) in the insulin signaling pathway, which in turn stimulated the activation of phosphoinositide 3-kinase (PI3K) and the phosphorylation of protein kinase B (Akt). The activation of PI3K and Akt by betulinic acid translocated glucose transporter 4 to the plasma membrane (PM-GLUT4), thereby increasing the expression of PM-GLUT4 and thus stimulating cellular glucose uptake. Betulinic acid also significantly increased the phosphorylation/activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. The activation of PI3K and AMPK by betulinic acid was confirmed using the PI3K inhibitor wortmannin and the AMPK inhibitor compound C. The increase in glucose uptake induced by betulinic acid was significantly decreased by wortmannin and compound C in the 3T3-L1 adipocytes. These results suggest that betulinic acid stimulates glucose uptake by activating PI3K and AMPK in 3T3-L1 adipocytes.

• CELLMED
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• v.4 no.4
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• pp.27.1-27.5
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• 2014

Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae) is a traditional Ayurvedic herb known as Kutki. It is used as a remedy for diabetes by tribes of North Eastern Himalayan region of India. Present study was conducted to explore the mechanism of antidiabetic activity of standardized aqueous extract of Picrorhiza kurroa (PkE). PkE (100 and 200 mg/kg/day) was orally administered to streptozotocin induced diabetic rats, for 14 consecutive days. Plasma insulin levels were measured and pancreas of rat was subjected to histopathological investigations. Glucose transporter type 4 (GLUT-4) protein content in the total membrane fractions of soleus muscle was estimated by Western blot analysis. Plasma insulin level was significantly increased along with concomitant increase in GLUT-4 content of total membrane fractions of soleus muscle of diabetic rats treated with extract. There was evidence of regeneration of ${\beta}$-cells of pancreatic islets of PkE treated group in histopathological examinations. PkE increased the insulin-mediated translocation of GLUT-4 from cytosol to plasma membrane or increased GLUT-4 expression, which in turn facilitated glucose uptake by skeletal muscles in diabetic rats.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.198-205
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• 2017

BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.

• 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.

• Molecules and Cells
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• v.23 no.3
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• pp.272-279
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• 2007

The maintenance of normal blood glucose levels at rest and during exercise is critical. The maintenance of blood glucose homeostasis depends on the coordination and integration of several physiological systems, including the sympathetic nervous system and the endocrine system. During prolonged exercise increased demand for glucose by contracting muscle causes to increase glucose uptake to working skeletal muscle. Increase in glucose uptake by working skeletal muscle during prolonged exercise is due to an increase in the translocation of insulin and contraction sensitive glucose transporter-4 (GLUT4) proteins to the plasma membrane. However, normal blood glucose level can be maintained by the augmentation of glucose production and release through the stimulation of liver glycogen breakdown, and the stimulation of the synthesis of glucose from other substances, and by the mobilization of other fuels that may serve as alternatives. Both feedback and feedforward mechanisms allow glycemia to be controlled during exercise. This review focuses on factors that control blood glucose homeostasis during prolonged exercise.