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ABSTRACT: Aim Glucagon-like peptide-1 (GLP-1) receptor participates in the control of bone resorption in GLP-1 knockout mice. Also, GLP-1 induces an insulin- and parathyroid hormone-independent osteogenic action through osteoclasts and osteoblasts in insulin-resistant and type 2 diabetic rats. Osteocytes are now considered central to bone homeostasis. A secreted product of osteocytes, sclerostin, inhibits bone formation. However, the effect of GLP-1 on osteocytes remains unclear. Therefore, we investigated the effect of GLP-1 on bone mineral density (BMD), and the cellular and molecular mechanisms associated with osteocytes. Main methods We investigated the presence of GLP-1 receptors in osteocyte-like MLO-Y4 cells and osteocytes of rat femurs through RT-PCR, Western blot and confocal microscopy, and investigated the effect of exendin-4 on the expression of mRNA (by quantitative real-time RT-PCR) and protein (by Western blot) of SOST/sclerostin in osteocyte-like MLO-Y4 cells during culture under normal or high-glucose (30mM) conditions, and measured circulating levels of sclerostin, osteocalcin, and tartrate-resistant alkaline phosphatase (TRAP) 5b and femoral BMD in type 2 diabetic OLETF rats treated with exendin-4. Key findings GLP-1 receptor was present on MLO-Y4 cells and osteocytes of rat femurs. Exendin-4 reduced the mRNA expression and protein production of SOST/sclerostin under normal or high-glucose conditions in MLO-Y4 cells. Exendin-4 reduced serum levels of sclerostin, increased serum levels of osteocalcin, and increased femoral BMD in type 2 diabetic OLETF rats. Significance These findings suggest that exendin-4 might increase BMD by decreasing the expression of SOST/sclerostin in osteocytes in type 2 diabetes.
Life sciences 01/2013; · 2.56 Impact Factor
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ABSTRACT: BACKGROUND: The identification and characterization of the gene, ERRFI1, in diabetes has not been reported. In this study, we evaluated the relationship between ERRFI1 polymorphism and characteristics of type 2 diabetes mellitus (T2DM) in Korea. SUBJECTS AND METHODS: We conduct a case-control study involving T2DM patients (n=342) and controls (n=473).RESULTS: A novel single nucleotide ERRFI1 gene polymorphism at +807(T/G) was found. G genotype frequency was 40.1% in the diabetic group and 42.7% in the control group; the difference was not significant (p=0.45). In the diabetic group, the urine albumin to creatinine ratio (ACR) was lower in the G genotype than in the T genotype (P=0.004). In males with T2DM, those with the G genotype displayed lower systolic blood pressure (P=0.01) and higher glomerular filtration rate (P=0.048) compare to those with the T genotype. In females with T2DM, urine ACR was low in those with the G genotype than in those with the T genotype (P=0.02). In the diabetic group, patients who harboring T allele had a 1.81 times higher risk of diabetic nephropathy than the G allele (95% CI 1.11-2.96, P=0.02). In females with T2DM, patients who harboring T allele had a 2.12 times higher risk of diabetic nephropathy (95% CI 1.07-4.1, P=0.03). CONCLUSIONS: We identify new loci associated with glycemic traits in diabetes and this finding indicates the potential of ERRFI1 as a novel therapeutic target of diabetic nephropathy.
Disease markers 01/2013; · 1.64 Impact Factor
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ABSTRACT: Estrogen (17β-estradiol) has been implicated in maintaining insulin sensitivity. It is thought to act predominantly through genomic pathways and regulate the expression of various genes via binding to estrogen receptors (ERs)-α and -β. 17β-estradiol has been reported to simultaneously stimulate protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK) in ex vivo skeletal muscle. Since data regarding the interaction between AMPK and the insulin receptor substrate-1 (IRS-1)/Akt pathway are controversial, the correlation between AMPK activation and insulin signaling remains unclear. In this study, we examined whether 17β-estradiol simultaneously stimulates the activation of AMPK and IRS-1/Akt in 3T3-L1 adipocytes as well as the 17β-estradiol-ER-induced interaction between the AMPK and IRS-1/Akt pathway in 3T3-L1 adipocytes not exposed to insulin. 17β-estradiol (10-7 M) rapidly activated AMPK and IRS-1/Akt in 3T3-L1 adipocytes, while the ER-α/β non-specific antagonist, ICI 182.780 (10 µM), and the AMPK antagonist compound C (20 µM) reversed the estrogen-induced activation of AMPK and tyrosine (Tyr)-IRS-1/Akt in these cells. Moreover, 17β-estradiol increased the expression of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), adiponectin, uncoupling protein 2 (UCP2) and glucose transporter 4 (GLUT4) genes 24 h after treatment, whereas the ER-α/β non-specific antagonist, ICI 182.780 (10 µM), and the AMPK antagonist compound C (20 µM) reversed the estrogen-induced increase in the expression of these genes. These results indicate that 17β-estradiol activates AMPK through an ER and activates Akt through AMPK activation in 3T3-L1 adipocytes, despite the absence of insulin. Furthermore, 17β-estradiol regulates the expression of genes related to glucose metabolism through ER-AMPK activation in these cells.
International Journal of Molecular Medicine 07/2012; · 1.98 Impact Factor
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ABSTRACT: Growth hormone insensitivity syndrome (GHIS), a genetic disease characterized by growth retardation combined with high serum concentration of growth hormone (GH) and low insulin-like growth factor 1 (IGF-1) levels, can be caused by mutations in the GH receptor (GHR) gene. We investigated the molecular defects in the GHR gene in a patient with neurofibromatosis type 1 (NF-1). The patient, a 2-year-old boy with NF-1, was assessed on his short stature by auxological, biochemical and molecular studies. Height of the patient and his family members were measured and compared to normal control. Serum concentrations of GH, IGF-1 and IGF-binding protein 3 (IGFBP3) in the patient were measured during a GH stimulation test. We examined the GHR gene in the patient and his parents. Genomic DNA and mRNA of the GHR gene were extracted from peripheral lymphocytes. All the exons and the flanking regions of the GHR gene were amplified by PCR, and directly sequenced. The patient's height was 75 cm (-2.89 SDS) with gradually reducing growth velocity, while the heights of the other family members were within the normal range. The GH stimulation test revealed that serum GH concentrations in the patient were much higher than those in the control group, and serum IGF-1 and IGFBP3 levels were extremely low. There was no germline mutation in the exons or the flanking regions of the patient's GHR gene. Interestingly, a deletion of 166 bases of exon 7 in the GHR mRNA was found, and it was suggested that the novel mutation resulted in premature termination (M207 fs. X8). This mutation decreases GH binding affinity to the GHR, and, thus, would be responsible for growth retardation.
International Journal of Molecular Medicine 06/2012; 30(3):713-7. · 1.98 Impact Factor
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ABSTRACT: Sleep disturbance has become an endemic behavior in modern countries, and its prevalence has also increased. Even a subtle sleep deficiency is related to health problems. Particularly, patients with pulmonary disease often complain of insomnia. We recently showed that sleep deprivation (SD) exacerbates existing acute lung inflammation, and that melatonin treatment attenuates it via anti-apoptotic and anti-oxidant action. In order to reinforce our previous report, the present study was designed to evaluate pro-inflammatory mediators in acute lung inflammation in SD mice. In addition, we investigated the infiltration of inflammatory cells into the lungs. Twenty-five ICR mice were divided into 5 groups (n=5/group): control, SD, lipopolysaccharide (LPS), LPS + SD and LPS + SD + melatonin. The SD mice were deprived of sleep for 96 h in a multiplatform water bath. LPS (5 mg/kg) and melatonin (5 mg/kg) were administered on day 2. The mice were sacrificed on day 3, and serum and bronchoalveolar lavage (BAL) fluid were collected. The serum levels of inflammatory cytokines were increased in the LPS + SD group. Interleukin-6, tumor necrosis factor-α and interferon-γ levels were also increased in BAL fluid in the LPS + SD group. Melatonin reduced inflammatory mediators in the serum and BAL fluid. The accumulation of leukocytes in the LPS and LPS + SD mice was elevated, however, melatonin inhibited the recruitment of inflammatory cells (p<0.05). Lymphocytes in the BAL fluid of the LPS + SD group were increased, and macrophage levels were decreased; however, the increment was attenuated by melatonin administration (p<0.05). In conclusion, this study indicates that melatonin has a protective effect against lung inflammation associated with SD.
Molecular Medicine Reports 02/2012; 5(5):1281-4. · 0.42 Impact Factor
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ABSTRACT: Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from β-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by β-cell exhaustion and apoptosis. ER stress induced by Ca(2+) depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear. Glucagon like peptide-1 (GLP-1) has anti-apoptotic effects in β-cells after the induction of oxidative and ER stress. In this study, we examined the anti-apoptotic action of a GLP-1 analogue in β-cell lines and islets against ER stress induced by chronic treatment of sulfonylurea. HIT-T15 and dispersed islet cells were exposed to glibenclamide for 48 h, and apoptosis was evaluated using Annexin/PI flow cytometry. Expression of the ER stress-related molecules and sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca(2+) concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca(2+) replenishing by SERCA restoration. These findings will further the understanding of one cause of glibenclamide-induced β-cell loss and therapeutic availability of GLP-1-based drugs in secondary failure by sulfonylurea during treatment of diabetes.
Journal of Pharmacological Sciences 12/2011; 118(1):65-74. · 2.08 Impact Factor
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ABSTRACT: Pinitol is thought to mediate insulin action and improve insulin resistance. We evaluated the effects of pinitol on glycemic control, insulin resistance and adipocytokine levels in type 2 diabetic patients.
A total of 66 patients with type 2 diabetes who had been taking oral hypoglycemic agents for at least 3 months were enrolled and randomized to receive pinitol (n = 33) or matching placebo (n = 33). All subjects took 1,200 mg pinitol or placebo and maintained their current oral hypoglycemic agents throughout the study.
Mean HbA1c, fasting plasma glucose, and HOMA-IR were significantly lowered more in patients taking pinitol than in those given a placebo. Patients who had an HbA1c over 8.0% showed a greater reduction (p < 0.01) than those who had an HbA1c below 8.0% (p =0.16). In addition, in the group of patients with a HOMA-IR over 2.5, there was a significant decrease in HbA1c compared to that in the group of patients with a HOMA-IR below 2.5. There were no differences in the changes in adiponectin, FFA and CRP between the two groups.
Pinitol can mediate insulin action to improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus, especially in patients with insulin resistance.
Annals of Nutrition and Metabolism 12/2011; 60(1):1-5. · 2.26 Impact Factor
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ABSTRACT: Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of β-cell mass through β-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of β-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from β-cell and differentiation to β-cell from progenitor cells. Also, it probably has an antiapoptotic effect on β-cell, but detailed mechanisms are not proven. Therefore, we examined the protective mechanism of GLP-1 in β-cell after induction of oxidative stress. The cell apoptosis decreased to ~50% when cells were treated with 100 µM H(2)O(2) for up to 2 hr. After pretreatment of Ex-4, GLP-1 receptor agonist, flow cytometric analysis shows 41.7% reduction of β-cell apoptosis. This data suggested that pretreatment of Ex-4 protect from oxidative stress-induced apoptosis. Also, Ex-4 treatment decreased GSK3β activation, JNK phosphorylation and caspase-9, -3 activation and recovered the expression of insulin2 mRNA in β-cell lines and secretion of insulin in human islet. These results suggest that Ex-4 may protect β-cell apoptosis by blocking the JNK and GSK3β mediated apoptotic pathway.
Journal of Korean medical science 11/2010; 25(11):1626-32. · 0.84 Impact Factor
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ABSTRACT: long-term ovariectomy-induced metabolic changes such as insulin resistance and glucose intolerance might be caused directly by estrogen deficiency and may occur partly as secondary effects of obesity arising due to the orexigenic effects of estrogen deficiency. Long-term estrogen treatment prevented those by exerting anorexigenic and metabolic actions in ovariectomized mice. However, the effect of short-term estrogen treatment on glucose metabolism in mice with short-term ovariectomy, during which ovariectomy-induced obesity does not develop, is not yet clear. The aim of this study was to evaluate the effect of short-term parenteral 17beta-estradiol treatment on glucose metabolism and blood glucose levels in mice at 2 weeks after ovariectomy, a time period during which ovariectomy-induced obesity does not develop.
we examined the effect of three 17beta-estradiol injections on fasting blood glucose levels, insulin resistance, components of the insulin signaling pathway, AMPK activation, and the expression of genes related to glucose metabolism in liver, skeletal muscle, and white adipose tissues of non-obese C57BL/6N mice with short-term ovariectomy.
three 17beta-estradiol injections decreased the fasting blood glucose levels, activated AMPK, and decreased the expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase and peroxisome proliferator-activated receptor-γ coactivator-1α in the liver. But three 17beta-estradiol injections did not affect insulin sensitivity and the components of the insulin signaling pathway in the liver and skeletal muscle.
short-term parenteral 17beta-estradiol treatment decreases the fasting blood glucose levels not via insulin sensitivity of the skeletal muscle in non-obese mice with short-term ovariectomy.
Life sciences 09/2010; 87(11-12):358-66. · 2.56 Impact Factor
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ABSTRACT: To assess the expressions of vascular endothelial growth factor (VEGF), fms-like tyrosine kinase-1 (Flt-1), and soluble Flt-1 (sFlt-1) genes in healthy normotensive and pre-eclamptic placentas of Korean women.
We investigated 12 healthy normotensive pregnant women and 10 pre-eclamptic pregnant women at Eulji University Hospital. The obtained placental tissues were analyzed using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction.
The sFlt-1 messenger ribonucleic acid (mRNA) level was elevated 2.6 times more in pre-eclamptic placentas than in normal control placentas. However, the VEGF mRNA level of pre-eclamptic placentas was decreased. There was no difference in the Flt-1 mRNA level between control and pre-eclamptic placentas.
Our study showed that expressions of genes relating to angiogenesis were altered in Korean pre-eclamptic placentas. These results suggest that the alteration in expressions of sFlt-1 and VEGF genes might be associated with the pathogenesis of pre-eclampsia.
Journal of Obstetrics and Gynaecology Research 08/2010; 36(4):726-32. · 0.94 Impact Factor
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ABSTRACT: Aim: To assess the expressions of vascular endothelial growth factor (VEGF), fms-like tyrosine kinase-1 (Flt-1), and soluble Flt-1 (sFlt-1) genes in healthy normotensive and pre-eclamptic placentas of Korean women.Methods: We investigated 12 healthy normotensive pregnant women and 10 pre-eclamptic pregnant women at Eulji University Hospital. The obtained placental tissues were analyzed using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction.Results: The sFlt-1 messenger ribonucleic acid (mRNA) level was elevated 2.6 times more in pre-eclamptic placentas than in normal control placentas. However, the VEGF mRNA level of pre-eclamptic placentas was decreased. There was no difference in the Flt-1 mRNA level between control and pre-eclamptic placentas.Conclusions: Our study showed that expressions of genes relating to angiogenesis were altered in Korean pre-eclamptic placentas. These results suggest that the alteration in expressions of sFlt-1 and VEGF genes might be associated with the pathogenesis of pre-eclampsia.
Journal of Obstetrics and Gynaecology Research 07/2010; 36(4):726 - 732. · 0.94 Impact Factor
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ABSTRACT: Monocyte chemoattractant protein-1 (MCP-1) plays a role in adipose tissue inflammation and insulin resistance. Human circulating MCP-1 concentrations reportedly increase or remain unchanged according to obesity or insulin resistance in various ethnic populations; whether or not circulating MCP-1 concentrations increase after menopause has remained unclear.
We investigated the relationship between circulating MCP-1 concentrations and obesity or insulin resistance, and the relationship between circulating MCP-1 and menopause status in premenopausal (n=111) and postmenopausal (n=64) Korean women.
Circulating MCP-1 concentrations were significantly higher in postmenopausal women than in obesity-matched premenopausal women; they did not differ between non-obese and obese subgroups of pre- and postmenopausal women. Circulating MCP-1 concentrations had a relationship with menopause status (rho=0.500, p=0.000), irrespective of obesity, but no relationship with obesity or insulin resistance. Circulating MCP-1 concentrations correlated with serum triglycerides (r=0.4, p=0.001) and also correlated with serum triglyceride concentrations, after adjusting for age and obesity, in postmenopausal women.
Circulating MCP-1 concentrations are associated with menopause status itself, irrespective of obesity; they do not correlate with obesity or insulin resistance in Korean women, most of whom are not severely obese.
Clinica chimica acta; international journal of clinical chemistry 03/2009; 403(1-2):92-6. · 2.54 Impact Factor
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Yang-Deok Lee,
Ju-Young Kim,
Ki-Ho Lee,
Yoon-Jin Kwak, Seong-Kyu Lee,
Ok-Soon Kim,
Dae-Yong Song,
Ji-Hye Lee,
Tai-Kyoung Baik,
Byung-Joon Kim,
Ji-Young Kim,
Haing-Woon Baik
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ABSTRACT: Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia. Recent studies have shown an association between sleep deprivation (SD) and inflammation, however, the underlying mechanisms remain unclear. In the present study, we investigated whether melatonin protects against acute lung inflammation in SD. Male ICR mice were deprived sleep using modified multiplatform water bath for 3 days. Acute lung inflammation was induced by lipopolysaccharide (LPS; 5 mg/kg). Melatonin (5 mg/kg) and LPS was administered in SD mice at day 2. Mice were divided into five groups as control, SD, LPS, LPS + SD, and LPS + SD + melatonin (each group, n = 11). Mice were killed on day 3 after treatment of melatonin and LPS for 24 hr. Lung tissues were collected for histological examination and protein analysis. The malondialdehyde (MDA) level was determined for the effect of oxidative stress. Melatonin restored weight loss in LPS + SD. Histological findings revealed alveolar damages with inflammatory cell infiltration in LPS + SD. Melatonin remarkably attenuated the alveolar damages. In western blot analysis, LPS reduced the levels of Bcl-XL and procaspase-3 in SD mice. After treatment with melatonin, the levels of Bcl-XL and procaspase-3 increased when compared with LPS + SD. LPS treatment showed an increase of TUNEL-positive cells, whereas melatonin prevented the increase of cell death in LPS + SD animals. In lipid peroxidation assay, melatonin significantly reduced the elevated MDA level in LPS + SD. Our results suggest that melatonin attenuates acute lung inflammation during SD via anti-apoptotic and anti-oxidative actions.
Journal of Pineal Research 08/2008; 46(1):53-7. · 5.79 Impact Factor
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ABSTRACT: The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m2) and BMI <25 kg/m2 groups in premenopausal females ( chi2=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.
Journal of Korean Medical Science 03/2008; 23(1):83-8. · 0.99 Impact Factor
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ABSTRACT: EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been shown to suppress cancer cell proliferation, and interfere with the several signaling pathways and induce apoptosis. Practically, there is emerging evidence that EGCG has a potential to increase the efficacy of chemotherapy in patients. We hypothesized that EGCG may exert cell cytotoxicity through modulating AMPK (AMP-activated protein kinase) followed by the decrease in COX-2 expression. EGCG treatment to colon cancer cells resulted in a strong activation of AMPK and an inhibition of COX-2 expression. The decreased COX-2 expression as well as prostaglandin E(2) secretion by EGCG was completely abolished by inhibiting AMPK by an AMPK inhibitor, Compound C. Also, the activation of AMPK was accompanied with the reduction of VEGF (vascular endothelial growth factor) and glucose transporter, Glut-1 in EGCG-treated cancer cells. These findings support the regulatory role of AMPK in COX-2 expression in EGCG-treated cancer cells. Furthermore, we have found that reactive oxygen species (ROS) is an upstream signal of AMPK, and the combined treatment of EGCG and chemotherapeutic agents, 5-FU or Etoposide, exert a novel therapeutic effect on chemo-resistant colon cancer cells. AMPK, a molecule of newly defined cancer target, was shown to control COX-2 in EGCG-treated colon cancer cells.
Cancer Letters 04/2007; 247(1):115-21. · 4.24 Impact Factor
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ABSTRACT: Epidemiologic and experimental evidences indicate that selenium, an essential trace element, can reduce the risk of a variety of cancers. Protection against certain types of cancers, particularly colorectal cancers, is closely associated with pathways involving cyclooxygenase-2 (COX-2). We found that AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, mediates critical anticancer effects of selenium via a COX-2/prostaglandin E(2) signaling pathway. Selenium activated AMPK in tumor xenografts as well as in colon cancer cell lines, and this activation seemed to be essential to the decrease in COX-2 expressions. Transduction with dominant-negative AMPK into colon cancer cells or application of cox-2(-/-)-negative cells supported the evidence that AMPK is an upstream signal of COX-2 and inhibits cell proliferation. In HT-29 colon cancer cells, carcinogenic agent 12-O-tetradecanoylphorbol-13-acetate (TPA) activated extracellular signal-regulated kinase (ERK) that led to COX-2 expression and selenium blocked the TPA-induced ERK and COX-2 activation via AMPK. We also showed the role of a reactive oxygen species as an AMPK activation signal in selenium-treated cells. We propose that AMPK is a novel and critical regulatory component in selenium-induced cancer cell death, further implying AMPK as a prime target of tumorigenesis.
Cancer Research 11/2006; 66(20):10057-63. · 7.86 Impact Factor
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ABSTRACT: Phytochemicals such as soy isoflavone genistein have been reported to possess therapeutic effects for obesity, diabetes, and cardiovascular diseases. In the present study, the molecular basis of selective phytochemicals with emphasis on their ability to control intracellular signaling cascades of AMP-activated kinase (AMPK) responsible for the inhibition of adipogenesis was investigated. Recently, the evolutionarily conserved serine/threonine kinase, AMPK, emerges as a possible target molecule of anti-obesity. Hypothalamic AMPK was found to integrate nutritional and hormonal signals modulating feeding behavior and energy expenditure. We have investigated the effects of genistein, EGCG, and capsaicin on adipocyte differentiation in relation to AMPK activation in 3T3-L1 cells. Genistein (20-200muM) significantly inhibited the process of adipocyte differentiation and led to apoptosis of mature adipocytes. Genistein, EGCG, and capsaicin stimulated the intracellular ROS release, which activated AMPK rapidly. We suggest that AMPK is a novel and critical component of both inhibition of adipocyte differentiation and apoptosis of mature adipocytes by genistein or EGCG or capsaicin further implying AMPK as a prime target of obesity control.
Biochemical and Biophysical Research Communications 01/2006; 338(2):694-9. · 2.48 Impact Factor
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ABSTRACT: Acinetobacter baumannii is an important opportunistic pathogen responsible for nosocomial infection. Despite considerable clinical and epidemiological data regarding the role of A. baumannii in nosocomial infection, the specific virulence factor or pathogenic mechanism of this organism has yet to be elucidated. This study investigated the molecular mechanism of apoptosis on the infection of human laryngeal epithelial HEp-2 cells with A. baumannii and examined the contribution of outer membrane protein 38 (Omp38) on the ability of A. baumannii to induce apoptosis of epithelial cells. A. baumannii induced apoptosis of HEp-2 cells through cell surface death receptors and mitochondrial disintegration. The Omp38-deficient mutant was not as able to induce apoptosis as the wild-type A. baumannii strain. Purified Omp38 entered the cells and was localized to the mitochondria, which led to a release of proapoptotic molecules such as cytochrome c and apoptosis-inducing factor (AIF). The activation of caspase-3, which is activated by caspase-9, degraded DNA approximately 180 bp in size, which resulted in the appearance of a characteristic DNA ladder. AIF degraded chromosomal DNA approximately 50 kb in size, which resulted in large-scale DNA fragmentation. These results demonstrate that Omp38 may act as a potential virulence factor to induce apoptosis of epithelial cells in the early stage of A. baumannii infection.
Cellular Microbiology 09/2005; 7(8):1127-38. · 5.46 Impact Factor
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ABSTRACT: This study was performed to observe the changes of glucose-related hormones and the morphological change including ultrastructure of the pancreatic islets in the male Otsuka Long-Evans Tokushima Fatty rat. Area under the curve (AUC) of glucose at the 30th (709 plus minus 73 mg.h/dL) and at the 40th week (746 plus minus 87 mg.h/ dL) of age were significantly higher than that at the 10th week (360 plus minus 25 mg.h/ dL). AUC of insulin of the 10th week was 2.4 plus minus 0.9 ng.h/mL, increased gradually to 10.8 plus minus 8.3 ng.h/mL at the 30th week, and decreased to 1.8 plus minus 1.2 ng.h/mL at the 40th week. The size of islet was increased at 20th week of age and the distribution of peripheral alpha cells and central beta cells at the 10th and 20th weeks was changed to a mixed pattern at the 40th week. On electron microscopic examination, beta cells at the 20th week showed many immature secretory granules, increased mitochondria, and hypertrophied Golgi complex and endoplasmic reticulum. At the 40th week, beta cell contained scanty intracellular organelles and secretory granules and apoptosis of acinar cell was observed. In conclusion, as diabetes progressed, increased secretion of insulin was accompanied by increases in size of islets and number of beta-cells in male OLETF rats showing obese type 2 diabetes. However, these compensatory changes could not overcome the requirement of insulin according to the continuous hyperglycemia after development of diabetes.
Journal of Korean Medical Science 03/2002; 17(1):34-40. · 0.99 Impact Factor
