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Original Articles
- The Effects of High Glucose, Insulin and TGF-beta 1 on Proliferation and Differentiation of the Pancreatic Stellate Cells.
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Oak Kee Hong, Hyuk Sang Kwon, Kyu Hyun Yeom, Marie Lee, Ji Hun Yang, Seung Hyeon Ko, Soon Jib Yoo, Hyun Sik Son, Kun Ho Yoon, Bong Yeon Cha, Kwang Woo Lee, Ho Yong Son, Sung Koo Kang
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Korean Diabetes J. 2003;27(3):228-240. Published online June 1, 2003
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Abstract
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- BACKGROUND
Although chronic pancreatitis gives rise to fibrosis of pancreatic exocrine tissue, and type 2 diabetes is accompanied by pancreatic fibrosis, the mechanisms of fibrogenesis in the pancreas have been insufficiently studied. The activated Pancreatic stellate cells (PSC) have recently been identified in human and experimental fibrotic areas from chronic panceatitis tissues. As PSC are similar in their morphology and biochemistry to hepatic stellate cells, they are suspected to play the same role in pancreatic fibrogenesis as the hepatic stellate cells in liver fibrosis. The PSC were isolated from the rat pancreata, and mediators stimulating the proliferation and differentiation identified. METHODS: The pancreatic stellate shaped cells were isolated by a minor modification to the method described by Apte et al (ref), using a Nycodenz gradient. The isolated PSCs were confirmed by phase-contrast and by the immunofluorescence of vimentin, desmin and smooth muscle a-actin (a-SMA). The level of alpha-SMA was quantified by Western blot in the PSCs in the culture, over time, and the cell proliferation was measured by 3[H]-Thymidine incorporation. The effect of the proliferation and differentiation of the PSC were assessed in relation to D-glucose (500 mg/dL), Insulin (10 IU/mL) and TGF-beta (10 ng/mL) treatment of the culture medium. RESULTS: The stellate shaped cells from the rat pancreata grew readily in the culture. Unactivated PSCs, cultured for 3 days, had an angular appearance, contained lipid droplets, manifesting positive vitamin A autofliuorescence, and stained positively for vimentin and desmin, but negatively for alpha-SMA. Within 4~8 days of primary culturing, the PSCs were activated, the sizes and numbers of the fat droplets decreased, the cells flattened, developed long cytoplasmic extensions and expressed alpha-SMA. After 3 passages, almost 100% of the cells were positive for alpha-SMA expression, indicating a myofibroblast type of differentiation in vitro. The addition of high-glucose concentrations and insulin to the activated PSCs significantly stimulated cell proliferation (194.4+/-8.3, 175.0+/-31.0 vs. control), and when the combination of high- glucose and insulin was applied, the cell proliferation was increased to an even greater extent (247.0+/-21.8 vs. control). CONCLUSIONS: Pancreata stellate cells can be isolated, and cultured in vitro, from normal SD rats. High concentrations of glucose and insulin in culture medium activated the PSC proliferation.
- Clustering of Risk Variables in Insulin Resistance Syndrome in Jungup District, Korea.
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Sang Wook Kim, Myung Hoe Huh, Young Il Kim, Jin Yub Kim, Eun Sook Kim, Moo Song Lee, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1999;23(6):843-856. Published online January 1, 2001
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Abstract
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- BACKGROUND
Insulin resistance syndrome (IRS), a clustering of hypertension, impaired glucose tolerance, low HDL cholesterol and high triglyceride, is prevalent in Korea. We studied the correlational structure of IRS using factor analysis to evaluate whether a single process underlies in the clustering of these risk factors. METHODS: Factor analysis was performed using data from 1,018 non-diabetic subjects (388 men and 630 women) who participated in the Jungup epidemiological study. RESULTS: Factor analysis reduced 9 correlated risk factors to 4 independent factors, each reflecting a different aspect of IRS: hypertension factor (increased systolic and diastolic blood pressure), glucose intolerance factor (increased fasting and postload glucose), obesity factor (increased body mass index, waist circumference, and increased insulin), and dyslipidemia factor (increased trigly- cerides and decreased HDL cholesterol). Increased insulin was also loaded into dyslipidemia factor in men and glucose intolerance factor in women. These factors explained about 70% of the total variance in the data. Three factors such as the glucose intolerance factor, the dyslipidemia factor and the obesity factor, were linked through mutual association with hyperinsulinemia, while hypertension factor was not associated with hyperin- sulinemia. Age-adjusted mean BP by BMI tertile and fasting insulin level tertile for men and women increased progressively with increase in BMI in men and women. There was no significant elevation of mean BP according to increase in fasting insulin level. In contrast to premenopausal women in whom hyperinsulinemia show mutual association with the glucose intolerance factor, the dyslipidemia factor, and the obesity factor, hyperinsulinemia was only loaded into obesity factor in postmenopausal women. CONCLUSION: These results suggested that more than one process underlies the clustering of IRS. In sulin resistance alone did not seem to be the single underlying mechanism of IRS. Especially, hypertension was not correlated with hyperin- sulinemia.
- Prevalence of Insulin Resistance Syndrome in Subjects Living in Jungup District , Korea.
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Sang Wook Kim, Jin Yub Kim, Eun Sook Kim, Young Il Kim, Moo Song Lee, Hyeong Ho Kim, Joong Yeoul Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1999;23(1):70-78. Published online January 1, 2001
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Abstract
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- BACKGROUND
The clustering of hypertension, impaired glucose tolerance, low HDL cholesteml and high triglyceride is known as insulin resistance syndrome (IRS). We studied the prevalence of insulin resistance syndrome among subjects living in Jungup district, Korea. METHODS: Among a total of 151,000 subjects over 40 years of years living in Jungup district, a sample of 1,791 was selected using a random cluster sampling method. Oral glucose tolerance test revealed 1,018 subjects with normal or impaired glucose tolerance. The IRS was defined as the coexistence of two or more components of triad; hypertension, impaired glucose tolerance and dyslipidemia (triglycerides >= 200mg/dL and HDL <45 mg/dL for woman, HDL < 35 mg/dL for men). RESULTS: Twenty-one percent of men and 45% of women were obese and 50.8% and 61.9% were hypertensive. Eleven percent of men and 16 percent of women were found to have dyslipidemia. The prevalence of impaired glucose tolerance was 10.2% for men and 15.7% for women. The prevalence of IRS in the Jungup population was 12.8% for men and 19.6% for women. The prevalence of IRS increased according to the plasma level of insulin. There was a positive correlation between the number of components of IRS and the level of fasting plasma insulin. CONCLUSION: We conclude that the prevalence of IRS is high in Korean subjects. The close correlation between the IRS components and fasting insulin level suggests that cardiovascular risk is associated with insulin resistance.
- The Characteristics of Insulin-resistance Syndrome in the Korean Population.
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Jin Sung Kim, Gun Sang Park, Yun Yong Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hyeon Kyu Kim, Yong Soo Park, Soon Ja Kwon
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Korean Diabetes J. 1998;22(1):84-92. Published online January 1, 2001
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Abstract
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- BACKGROUND
Insulin-resistance syndrome or syndrome X which includes diabetes mellitus, hypertension, dyslipidemia, and obesity has been regarded as one of the mechanisms involved in the atherosclerotic disease. This study was performed to evaluate the prevalence of each camponent of insulin-resistance syndrome. We have also analyzed the clustering of insulin-resistance syndrome according to fasting insulin levels in subjects who participated in the Younchon county diabetes prevalence study in 1993. METHOD: One thousand, eight hundred and eleven subjects among 2520 subjects over 30 years-old were enrolled, We investigated the prevalence of 5 metabolic syndromes: glucose intolerance(impaired glucose tolerance and diabetes mellitus by WHO criteria), hypertension(diastolic blood pressure >95 mmHg), Hypertriglyceridemia(triglyceride >2.26 mmol/L), low HDL cholesterolemia(HDL cholesterol <0.91 mmol/ L) and obesity(body mass index >25 kg/m) according to fasting serum insulin level. RESULTS: The prevalence of glucose intolerance (diabetes mellitus and impaired glueose tolerance), hypertension, hypertriglyceridemia, low HDI, cholesterolemia and obestiy were 18.2%, 21.3%, 10.9%, 45.6% and 36.3%, respectively. According to the four quartiles(quartile 1, 2, 3, 4) of fasting serum insulin level, the prevalence rate of each metaboic syndrome was as follows: 9.5%, 15.6%, 22.8% and 25.0% for glucose intolerance; 18.7%, 17.5%, 21.1% and 27.9% for hypertension; 5.0%, 8.1%, 13 8% and 16.9% for hypertriglyceridemia; 37.9%, 46.6%, 46.5% and 51.6% for low HDL cholesterolemia; 19.2%, 30.1%, 40.8% and 55.4% for obesity. As the fasting insulin levels increase, the clustering of 2 or more disease increase. CONCLUSION: Metabolic syndromes associated with insulin-resistance are relatively common disorders in the Korean population. The prevalence and clustering of metabolic abnormalities also increase as serum insulin level increases in Korean population.
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