- The Effect of Chronic High Glucose Concentration on Endoplasmic Reticulum Stress in INS-1 Cells.
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Mi Kyung Kim, Hye Young Seo, Tae Sung Yun, Nam Kyung Kim, Yu Jin Hah, Yun Jung Kim, Ho Chan Cho, Young Yun Jang, Hye Soon Kim, Seong Yeol Ryu, In Kyu Lee, Keun Gyu Park
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Korean Diabetes J. 2008;32(2):112-120. Published online April 1, 2008
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DOI: https://doi.org/10.4093/kdj.2008.32.2.112
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Abstract
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- BACKGROUND
The highly developed endoplasmic reticulum (ER) structure is one of the characteristic features of pancreatic beta-cells. Recent study showed that ER stress causes beta-cell dysfunction. However, little is known about the effects of high glucose concentration on induction of ER stress in pancreatic beta-cells. Therefore, this study was designed to evaluate whether exposure of high glucose concentration in rat insulinoma cell line, INS-1 cell induces ER stress and whether ER stress decreases insulin gene expression. METHODS: The effect of 30 mM glucose on insulin expression and secretion in INS-1 cells was evaluated by Northern blot analysis and glucose-stimulated insulin secretion (GSIS). Cell viability was evaluated by XTT assay. The effect of 30 mM glucose on phosphorylation of eIF2alpha and CHOP expression, which are markers of ER stress were evaluated by Western blot analysis. RT-PCR analysis was performed to determine whether high glucose concentration induces XBP-1 splicing. To investigate whether ER stress decreases insulin gene expression, the effect of tunicamycin on insulin mRNA expression was evaluated by Northern blot analysis. RESULTS: The prolonged exposure of INS-1 cells with the 30 mM glucose concentration decreased insulin mRNA expression in a time dependent manner and impaired GSIS while did not influence on cell viability. 30 mM glucose increased phosphorylation of eIF2alpha, XBP-1 splicing and CHOP expression in INS-1 cells. Tunicamycin-treated INS-1 increased XBP-1 splicing and decreased insulin mRNA expression in a dose dependent manner. CONCLUSION: This study showed that prolonged exposure of INS-1 with high glucose concentration induces ER stress and ER stress decreases insulin gene expression. Further studies about underlying molecular mechanism by which ER stress induces beta-cell dysfunction are needed.
- A Case of Cured Diabetes Mellitus after Occult Malignant Pheochromocytoma Removal.
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Ho Chan Cho, Hye Soon Kim, Yoon Jung Kim, Yu Jin Hah, Nam Keong Kim, Mi Kyung Kim, Keun Gyu Park, Yong Hoon Kim, Sun Young Kwon
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Korean Diabetes J. 2007;31(6):520-524. Published online November 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.6.520
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Abstract
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- Pheochromocytoma is characterized by a combination of various clinical manifestations that include the classic triad of severe headache, palpitations and diaphoresis. In addition, hyperglycemia can be caused by overproduction of catecholamines, which are secreted by a catecholamine-secreting neoplasm of adrenal or extra-adrenal chromaffin tissue. We encountered a case of diabetes with an occult malignant adrenal pheochromocytoma, who did not have any classic manifestations. A 37-year-old male was admitted because of polydipsia, polyuria, and weight loss. Fasting blood glucose level was 497 mg/dL, hemoglobin A1c level was 15%, and diabetic retinopathy and peripheral polyneuropathy were also accompanied. Incidentally, right adrenal mass was detected by ultrasonography of abdomen. Urinary excretion of total metanephrine and epinephrine were elevated. Adrenal CT showed a 7.1 cm sized right adrenal cystic mass with enhancing solid portion and hemorrhagic content. The scan with 123I-MIBG revealed the cystic mass with increased rim uptake in the region of right adrenal gland. After removal of the tumor, the increased levels of catecholamine were normalized. Moreover, blood glucose level was normalized without administration of insulin or oral hypoglycemic agents. The pathologic examination showed that the neoplasm was a malignant adrenal pheochromocytoma. We report this case that diabetes was cured after removal of malignant tumor with literature review at first in Korea.
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- Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis
Chai Ryoung Eun, Jae Hee Ahn, Ji A Seo, Nan Hee Kim Endocrinology and Metabolism.2014; 29(1): 83. CrossRef
- The Effect of alpha-lipoic Acid on Endothelial Dysfunction Induced by Intralipid Infusion in Healthy Volunteers.
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Dong Wook Lee, Mi Jung Kim, Hye Soon Kim, Tae Sung Yun, Ho Chan Cho, Sang Jun Lee, Seung Ho Hur, Kyo Cheol Mun, Yong Won Cho, Jae Hoon Bae, In Kyu Lee
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Korean Diabetes J. 2002;26(5):336-346. Published online October 1, 2002
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Abstract
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- BACKGROUND
Endothelial dysfunciton has been proposed as an early manifestation of atherogenesis. Recently, emerging evidence suggests that hypertriglyceridemia and elevated free fatty acid are important risk factors in the development of atherosclerosis, probably through an increased oxidative stress. To clarify the hypothesis, we evaluated the effect of alpha-lipoic acid (ALA) on the endothelial dysfunction induced by intralipid infusion in healthy volunteers. METHODS: Hypertriglyceridemia and elevated free fatty acids was induced by infusion of intralipid. FMD (Flow-mediated dilation) of the brachial artery was investigated noninvasively by a high-resolution ultrasound technique in 13 young, healthy men without risk factors for coronary heart disease. RESULTS: Plasma triglyceride, free fatty acid and the superoxide anion were increased from 61.7+/-28.8 to 332.6+/-202.5 mg/dL, from 330.7+/-131.1 to 1267.0+/-486.2 microEq/L and from 6.6+/-2.2 to 8.7+/-1.5 X 10(-7)nmol/10(6)cells/30min (vs. basal p<0.001), respectively, following infusion of the intralipid. The FMD was decreased from 10.1+/-3.3 to 7.7+/-3.7% (vs. basal p<0.01) following infusion of the intralipid. After treatment with ALA, the increase in the FMD and the decrease in superoxide anion were significant. CONCLUSION: Acute hypertriglyceridemia, induced by intralipid infusion, is implicated in endothelial dysfunction. This endothelial dysfunction was reversed by treatment with ALA. These results suggest that chronic and repeated hypertriglyceridemia may play important roles in the development of atherosclerosis probably by increasing oxidative stress.
- The Effect of Alpha-lipoic Acid on Endothelial Dysfunction in Postmenopausal Uncomplicated Type 2 Diabetes.
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Ho Chan Cho, Sang Jun Lee, Mi Jung Kim, Hye Sun Kim, Tae Sung Yun, Sung Jae Kim, Sang Hyon Kim, Seung Ho Hur, Kyo Chul Moon, Jae Hoon Bae, In Kyu Lee
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Korean Diabetes J. 2002;26(4):242-252. Published online August 1, 2002
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Abstract
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- BACKGROUND
Recently, increased oxidative stress has been proposed as a major cause of vascular complications of patients with diabetes mellitus. Increased generation of oxygen free radicals in patients with diabetes mellitus could deplete cellular antioxidants and inactivate endothelial dependent vasodilating factor (EDRF), such as nitric oxide (NO). The purpose of this study was to evaluate whether the antioxidant alpha-lipoic acid (ALA) is effective in endothelial dysfunction of brachial artery, which induced by increased oxidative stress in postmenopausal diabetic women using high resolution ultrasound technique and initial reaction time (IRT) measurement. METHODS: We enrolled 11 menopausal women (mean age, 56.5+/-5.1 years) with uncomplicated type 2 diabetes. All patients were taking 1200 mg of ALA (Thioctacid(R), Bukwang, Korea). We measured of superoxide anion (O2-) in neutrophils as a marker of oxidative stress. Flow-mediated dilation (FMD) was measured using a high-resolution ultrasound. RESULTS: After treatment of ALA, fasting blood glucose was decreased significantly, the endothelium-dependent vasodilation of the brachial artery was increased, and O2- production was also decreased significantly. CONCLUSION: These results show that short term ALA treatment could improve the endothelial dysfunction in patients with type 2 diabetes mellitus. This improvement might be related with the antioxidants effect of ALA.
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