• Korean Journal of Pharmacognosy
• /
• v.36 no.4 s.143
• /
• pp.291-298
• /
• 2005

Anti-hyperglycemic effects of 17 medicinal plants that have been used for ameliorating diabetes in oriental medicine were evaluated using glucose transport assay in 3T3-L1 adipocytes. Higher activities were obtained by treating water or alcohol extract of Phellodendri Cortex (PC), which showed enhancing effects both on basal and insulin-stimulated glucose uptake. The latter effect of PC was completely inhibited by wortmannin, a specific inhibitor for phosphatidyl inositol 3-kinase (PI 3-kinase), but not affected by SB203580, A specific inhibitor for p38 mitogen-activatedprotein kinase(MAPK). Genistein, an inhibitor for tyrosine kinases, abolished the PC effects completely. Treatment of vanadate, an inhibitor for tyrosine phosphatases, together with PC showed no significant synergic enhancement in glucose uptake. The results of inhibitors associated with insulin signaling pathway indicated that extracts of PC enhance glucose uptake by PI-3 kinase activation which is an upstream event for GLUT4 translocation. Antidiabetic effects of PC extract might be also due to enhanced tyrosine phosphorylation and reduced tyrosine dephosphorylation. In addition, PC accelerated insulin-stimulated glucose uptake in insulin-resistant cells, recovering the uptake level close to that of normal cells. These findings may offer a new way to utilize extracts of PC as novel anti-hyperglycemic agents.

• Reproductive and Developmental Biology
• /
• v.33 no.4
• /
• pp.211-216
• /
• 2009

A cell frequently utilizes glucose as a fuel of energy and a major substrate of lipid and protein syntheses. A regulation of glucose movement into and out of the cells is precisely controlled by cooperative works of passive and sodium-dependent active processes. At least 13 glucose cotransporter (Slc2a, GLUT) isoforms involve in passive movement of glucose in cells. The efferent ductules (EDs) play in a number of important functions for maintenance of male fertility. In the present study, using real-time PCR analysis, we determined gene expression of five Slc2a isoforms in the EDs. In addition, we compared expression levels of these Slc2a isoforms according to postnatal development ages, 1 week, 2 weeks, 1 month, and 3 months. Results from the current study showed that expression of Slc2a1, Slc2a3, and Slc2a5 mRNAs reached the highest levels at 1 month of age, followed by a transient decrease at 3 months of age. In addition, the level of Slc2a4 mRNA reminded at steady until 1 month of age and was significantly reduced at 3 months of age, whereas the highest level of Slc2a 8 mRNA was detected at 2 weeks of age. Data from the present study indicate a differential expression of various Slc2a isoforms in the ED according to postnatal ages. Thus, it is believed that glucose movement through the epithelial cells in the ED would be regulated by the coordinated manner among Slc2a isoforms expressed at a given age.

• Journal of Animal Science and Technology
• /
• v.51 no.6
• /
• pp.493-502
• /
• 2009

Glucose is a major source of metabolic fuel and lipid and protein syntheses. Transport of glucose into the cell is regulated by an action of glucose transport.associated transporters, especially solute carriers 2A (Slc2a, protein symbol GLUT). The present study was focused on examination of mRNA expression of various Slc2a isoforms in the epididymis during postnatal development. Total RNAs isolated from different epididymal segments (caput, corpus, and caudal epididymis) were utilized for real-time polymerase chain reaction analyses. Results showed that Slc2a 1, 3, 4, 5, and 8 were expressed in the entire epididymal regions. In addition, the abundance of these Slc2a isoforms' transcripts was different within each epididymal regions. Moreover, the present study showed differential expression of these Slc2a isoforms among different epididymal segments according to postnatal ages. The current study suggests that glucose transport in the epididymis via various Slc2a isoforms would be necessary for maintenance of the epididymal functions.

• Molecules and Cells
• /
• v.19 no.1
• /
• pp.31-38
• /
• 2005

Human embryonic stem (hES) cells have unique features including unlimited growth capacity, expression of specific markers, normal karyotypes and an ability to differentiate. Many investigators have tried to use hES cells for cell-based therapy, but there is little information about the properties of available hES cell lines. We compared the characteristics of three hES cell lines. The expression of SSEA-1, -3, -4, and APase, was examined by immunocytochemistry, and Oct-4 expression was analyzed by RT-PCR. Differentiation of the hES cells in vitro and in vivo led to the formation of embryoid bodies (EBs) or teratomas. We examined the expression of tissue-specific markers in the differentiated cells by semiquantitative RT-PCR, and the ability of each hES cell line to proliferate was measured by flow cytometry of DNA content and ELISA. The three hES cell lines were similar in morphology, marker expression, and teratoma formation. However there were significant differences (P < 0.05) between the differentiated cells formed by the different cell lines in levels of expression of tissue-specific markers such as renin, kallikrein, Glut-2, ${\beta}-$ and ${\delta}-globin$, albumin, and ${\alpha}1-antitrypsin$ (${\alpha}1-AT$). The hES cell lines also differed in proliferative activity. Our observations should be useful in basic and clinical hES cell research.

• Journal of the East Asian Society of Dietary Life
• /
• v.24 no.3
• /
• pp.335-350
• /
• 2014

Compared to the large numbers of studies on the diabetes, hyperlipidemia and cancer therpeutic effects of ginseng, the anti-obese effect and mechanisms of ginsengs have not been studied as much. To determine the effects of ginseng on obesity, 14 keywords (ginseng, ginsenoside, obesity, weight, fat, diet, overeat, appetite, lipid, 3T3-L1, adipocyte, food intake, adipogenesis and lipolysis) were combined in searching a database. Fifty-six articles published from 1983 to 2012 as well as 656 patents registered until Aug $17^{th}$, 2012, were screened for anti-obese effects of ginseng. In the classification of experimental methods, 16 papers on 3T3-L1 cells, 38 papers on animals and three papers on human were reviewed. In terms of obese mechanisms of action, the most commonly used biomarkers were in order of lipid profiles > weight change > blood glucose > adipocytokine. Most ginseng studies on obesity focused on AMPK, $PPAR{\gamma}$, GLUT-4, PI3K and SREBP-1. Korean white ginseng extracts and Re repressed the lipogenesis genes such as PPARc2, SREBP-1c, LPL, FAS and DGAT1. However, ginseng or ginsenosides, PD (Rb1) and PT (Re), showed different or contradictory results. Water and ethanol extraction of ginseng showed contradictory effects on the secretion of inflammatory cytokines, wheras IL-6 was repressed by ethanol extracts and TNF-${\alpha}$ repressed by Re in vitro. Based on the literature, further studies on anti-obese mechanisms of ginseng, such as the inflammation-related obesity or cross signals between the adipocytes and the environments, are needed, instead of more studies on its hypolipidemic and hypoglycemic effects.

• The Korean Journal of Physiology and Pharmacology
• /
• v.12 no.1
• /
• pp.7-12
• /
• 2008

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium $(K_{ATP})$ channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of $K_{ATP}$ channels, insulin receptor ${\beta}$-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that $K_{ATP}$-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on $K_{ATP}$ channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

• Food Science and Biotechnology
• /
• v.17 no.6
• /
• pp.1146-1150
• /
• 2008

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.

• Molecules and Cells
• /
• v.44 no.10
• /
• pp.710-722
• /
• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.4
• /
• pp.341-354
• /
• 2021

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

• Herbal Formula Science
• /
• v.27 no.3
• /
• pp.223-236
• /
• 2019

Dengropanax morfiferus (D), Broussonitia kazinoki (B), and Cudriania tricuspidata (E), a widely cultivated species in South Korea, has been used as traditional medicine to treat numerous diseases. In this study, we evaluated the antidiabetic effects in a various signaling mechanisms using mixed extract and major component contents were analyzed by HPLC in the combined extracts from Dengropanax morfiferus, Broussonitia kazinoki, and Cudriania tricuspidata (DBCE). DBCE inhibited ${\alpha}$-glucosidase and ${\alpha}$-amylase activation and showed potent antioxidant effects, which are evaluated using DPPH, ABTS, and SOD assay. Cytokines, which are released by inflammatory cells in pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. DBCE showed the protective effects in RINm5F cells against cytokines-induced damage by suppressing inducible nitric oxide (NO) synthase and COX-2 expression and NO production. Insulin resistance is the primary characteristic of type 2 diabetes. Therefore, the regulatory effect of DBCE on glucose uptake and production are investigated in insulin-responsive human HepG2 cells. DBCE stimulated glucose uptake, prevented Glut2 and phosphor-IRS1 downregulation induced by high glucose (HG, 30 mM). Moreover, DBCE pretreatment diminished glucose levels, PEPCK and G6Pase overexpression provoked by HG. These findings suggest that DBCE might be used for diabetes treatment through alpha-glucosidase or alpha-amylase activity regulation, pancreatic beta cell protection, hepatic glucose sensitivity improvement. Cytokines, which are released by inflammatory cells' infiltrations around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus.