- Effects of Caloric Restriction on the Expression of PGC-1 and PPARs mRNA in Liver of Otsuka Long-Evans Tokushima Fatty Rats.
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Sang Yong Kim, Jin Hwa Kim, Hak Yeon Bae, Byoung Rai Lee
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Korean Diabetes J. 2006;30(3):161-169. Published online May 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.3.161
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 Abstract
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- BACKGROUND
Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. PPARgamma-coactivator 1 (PGC-1) and Peroxisome proliferator -activated receptors (PPARs) costimulate the expression of key enzymes of gluconeogenetic pathway. This study was performed to evaluate the response to dietary caloric restriction (CR) on the PPARs and PGC-1 expression in liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: Diabetic OLETF rats (male, 24 weeks) and Long-Evans Tokushima Otsuka (LETO) rats (male, 24 weeks) were used in this study. Liver PPARs and PGC-1 mRNA, and blood glucose levels were investigated at 1, 2, and 3 weeks after the beginning of 30% CR. PPARs and PGC-1 mRNA were determined by RT-PCR and blood glucose levels were measured by spectrophotometric assay. RESULTS: The liver PGC-1 mRNA expressions were increased to 19% in non-diabetic LETO rats but significant change was not observed in diabetic OLETF rats by 30% CR. The liver PPARgamma mRNA expressions were not changed in non-diabetic LETO rats but increased to 23% in diabetic OLETF rats by 30% CR. The difference of PPARalpha and PPARbeta mRNA expressions in liver of OLETF and LETO rats were not observed. CONCLUSION: The liver PPARgamma and PGC-1 expression response to CR are altered in OLETF rats compared to in LETO rats. These findings suggested that PPARgamma and PGC-1 expression control system altered in diabetic OLETF rat liver and altered PPARgamma and PCG-1 expression may some roles on the aberrantly activated gluconeogenesis in diabetes mellitus.
- Increased ROS Production by High Glucose in Cultured Mouse Insulinoma Cell Line.
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Jin Hwa Kim, Jung In Kim, Dong Hyun Choi, Young Uk Seo, Young Dae Kim, Jong Chan Oh, Beom Ju Lee, Keo Woon Park, Sang Yong Kim, Hak Yoen Bae, Byoung Rai Lee
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Korean Diabetes J. 2004;28(4):273-283. Published online August 1, 2004
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Abstract
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- BACKGROUND
To investigate the effects of high glucose on oxidative stress of islet beta cells, the effects of high glucose on antioxidant enzymes, the production of free reactive substances and paraquat-induced cytotoxicity were examined in cultured mouse insulinoma cells (MIN6N8a). METHODS: The MIN6N8a cell line (Obtained from Diabetic research center, Univer sity of Calgary, Canada) was maintained in RPMI1640 medium supplemented with 10% fetal bovine serum, at 37degrees C under an atmosphere of 5% CO2 and 100 % humidity. The MIN6N8a cells were cultured in high glucose (22.4 mM) and normogl-ucose (5.6 mM) containing RPMI1640 media, for 1-6 days, and the superoxide dismutase (SOD), catalase and glutathione peroxidase (GSHPx) activities in the MIN6N8a cells assayed. The levels of reactive oxygen species in the MIN6N8a cells was determined using dihydroethidium (DHE). Paraquatinduced cytotoxicity was determined using the 3-[4,5-dimethylthiazol-2-yl]-2, 5diphenyl tetraz olium bromide (MTT) method. RESULTS: No difference was observed catalase in the catalase and GSHPx activities in MIN6N8a cells between the high glucose (22.4 mM) and normoglucose (5.6 mM) groups. The CuZn-SOD activity of MIN6N8a cells was decreased by 32% in the high glucose (25.4 mM) medium compared to normoglucose (5.6 mM) medium, while the Mn-SOD activity was increased by 24% in high glucose group. The paraquat induced cytotoxicity of MIN6N8a cells was potentiated by high glucose. and the amount of DHE oxidation increased. CONCLUSION: The Oxidative stress in MIN6N8a cells was increased by high glucose as a resulted of the decreased CuZn-SOD activity and increased production of reactive oxygen species. Increased oxidative stress in MIN6N8a cells by high glucose may play some roles in the pathogenesis of diabetes.
- Effects of Gutathione on Cyclosporine A-induced Cyotoxicity in Cultured Rat Insulinoma (RIN5mF) Cells.
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Dong Hyun Choi, Byoung Rai Lee, Dai Yong Jang, Jong O Kim, Byung Soo Kim, Ki Young Chung, Tae Young Lim, Byung Chul Shin, Hak Yeon Bae
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Korean Diabetes J. 2002;26(1):58-64. Published online February 1, 2002
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Abstract
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Cyclosporin A (CsA) is a immunosuppressive agent that is most widely used in organ transplanted patients to prevent immunorejection, However, it has some side effects, including diabetes mellitus, nephrotoxicity and hypertension. The mechanism of CsA cytotoxicity is unclear but it has been suggested that reactive oxygen species are involved in the cytotoxic reactions. The purpose of this study was to determine the effects of glutathione, as a physiological antioxidant on CsA induced beta-cell toxicity. METHODS: Rat insulinoma (RINm5F) cells were incubated with culture media (RPMI1640) in the presence of CsA and/or buthionine sulfoximine (BSO), which is an inhibitor of r-glutamyl cysteine synthetase, and reduced glutathione. The viable cells were examined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and was determined by a spectrophotometer at a wavelength of 570 nm. RESULTS: Incubating the RINm5F cells with CsA resulted in a decrease in cell viability with increasing dose. This deceased cells viability, induced by CsA was potentiated by BSO treatment. The CsA and BSO induced cells toxicity was reduced significantly by the reduced glutathione. CONCLUSION: The results suggest that pancreatic beta-cell may be injured by CsA and glutathione may have some role in cytotoxicity.
- Changes of TBARS and GGTase in Ischemia / Reflowed Kidney of Alloxan-diabetic Rat.
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Jong Hoon Chung, Hak Yeon Bae, Jong Hee Cha, Jae Yoon Park, Pyoung Sim Park, Kwang Sam Koh, Byoung Rai Lee
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Korean Diabetes J. 1999;23(6):777-784. Published online January 1, 2001
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Abstract
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To investigate the influence of diabetes mellitus (DM) on ischemia/reflow injury, the contents of thiobarbituric acid reactive substance (TBARS: marker of peroxidative cell injury), and the activity of gamma-glutamyltransferase (GGTase: marker of brush border membrane injury) were measured in ischemia/reflowed kidney of diabetic rats. METHODS: Rats were divided into the 3 groups; control (C), diabetes for 2 weeks (DM2) and diabetes for 4 weeks (DM4), and DM was induced by alloxan (80 mg/kg ip). Left kidney was subjected to 30 min of ischemia and 15 min of blood reflow, and the right kidney was used as a control kidney. The activities of antioxidant enzymes and GGTase, and the contents of TBARS were determined in kidney homogenate. RESULT: Catalase activity in ischemia/reflowed kidney was decreased 20% (p<0.05) in C, 34% (p<0.01) in DM2 and 23% (p<0.01) in DM4, while the change of SOD and GSHPx activities were not observed in kidney of diabetic rats cornpared with group C. TBARS contents, when ischemia/reflow, increased by 23% in C, 19% (p<0.01) in DM2, 16% in DM4, while the activity of GGTase decreased by 40% i#n C, 54% in DM2, and 55% (p<0.01) in kidney of DM4. CONCLUSION: The TBARS contents in ischemia/ reflow kidney of diabetic group showed no change, while GGTase activity was decreased significantly when compared with control group. This study may suggested that in ischemia/reflow kidney, the peroxidative membrane lipid injury was not increased, but the brush border membrane injury was increased by DM.
- Plasma Paraoxonase Activities in Type 2 Diabetes Mellitus.
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Gyoung Mu Her, Hak Yeon Bae, Byoung Rai Lee
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Korean Diabetes J. 1998;22(3):403-409. Published online January 1, 2001
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Abstract
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- BACKGROUND
Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphate and possibly in the prevention of LDL lipid peroxidation. The activities of paraoxonase and levels of HDL cholesterol were measured in the serum of individuals with type 2 diabetes mellitus in order to evaluate whether a correlation exists between these cnzyme activities and the diabetes mellitus and dliabetic complications. METHODS: Plasma samples were obtain from 60 individuals with type 2 diabetes mellitus(32 women and 28 men; mean age=55.8 yrs) and 30 individuals with healthy control(16 women and 14 men; mean age=-54.1 yrs). Paraoxonase activities were measured spectrophotometrically in 0.1IM Tris-HC1 buffer(pH= 7.4) at 25C with paraoxon as substrate(5.5mM) at 405nm. RESULTS: No significant differences of plasma paraoxonase activity between healthy control and type 2 diabetes mellitus were observed. The significant difference of plasma paraoxonase activity between healthy control and type 2 diabetes mellitus with diabetic complications such as diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were observed. The difference of plasma paraoxonase activity between individuals with type 2 diabetes mellitus without diabetic complication and type 2 diabetes mellitus with diabetic complications was significant. The correlation between paraoxonase activity and HDL-cholesterol, plasma lipoproteins, HbAlc and duration of diabetes were not observed. CONCLUSION: These experimental results suggested that the plasma paraoxonase activity wasnt decreased in individuals with type 2 diabetes mellitus without diabetic complication and the decrement of plasma paraoxonase activity was might be associated with diabetic chronic complications.
- The Effect of High Glucose on the Activity of Superoxide Dismutase in NIN6N8a Cells.
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Hak Yeon Bae, Byoung Rai Lee, Kwang Sam Kho
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Korean Diabetes J. 1998;22(3):271-289. Published online January 1, 2001
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Abstract
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Reactive oxygen species play a role in the pathogenesis of diabetes mellitus. Hyperglycemia may cause increased production of free radicals, and peroxide formation was increased in high glucose solution. It has been demonstrated that active oxygen species induce antioxidant enzyme expression in some tissues and cells. This study was designed to investigate the effect of high glucose on the activity of superoxide dismutase(SOD) in mouse insulinoma(MIN6N8a) cells. METHODS: MIN6N8a cells were grown in RPMI1640 medium with l0% fetal bovine serum and NIH3T3 cells used as a control cells. The cells were cultured in 5.6 and 22.2 mM glucose cnntained medium. The activities of SOD, catalase and GPX were determined in crude cell extract after 7 days of culture. The levels of CuZn-SOD were also measured with ELISA using anti-CuZn-SOD antibody. RESULTS: In MIN6NSa cells, the catalase activity was very low compared with NIH3T3 cells, but there was no difference in activities of CuZn-SOD and GPX between MIN6N8a cells and NIH3T3 cells. The activity of CuZn-SOD was decreased, while Mn-SOD was increased in MIN6NSa cells cultured with high glucose(22.2 mM) medium compared with those of normoglucose(5.6 mM) medium. However, the level of CuZn-SOD in MIN6NSa cells, when measured with ELISA was high in cells of cultured with high glucose medium. The SOD activity was not effected in MIN6N8a cells cultured with insulin contained medium. CONCLUSION: These experimental result suggest that the CuZn-SOD activity was decreased in MIN6N8a cells cultured with high glucose contained medium and this effect may be resulted from the protein inactivation rather than decrement of protein level.
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