• Title/Summary/Keyword: insulin

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Recent advances in organoid culture for insulin production and diabetes therapy: methods and challenges

  • Dayem, Ahmed Abdal;Lee, Soo Bin;Kim, Kyeongseok;Lim, Kyung Min;Jeon, Tak-il;Cho, Ssang-Goo
    • BMB Reports
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    • v.52 no.5
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    • pp.295-303
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    • 2019
  • Breakthroughs in stem cell technology have contributed to disease modeling and drug screening via organoid technology. Organoid are defined as three-dimensional cellular aggregations derived from adult tissues or stem cells. They recapitulate the intricate pattern and functionality of the original tissue. Insulin is secreted mainly by the pancreatic ${\beta}$ cells. Large-scale production of insulin-secreting ${\beta}$ cells is crucial for diabetes therapy. Here, we provide a brief overview of organoids and focus on recent advances in protocols for the generation of pancreatic islet organoids from pancreatic tissue or pluripotent stem cells for insulin secretion. The feasibility and limitations of organoid cultures derived from stem cells for insulin production will be described. As the pancreas and gut share the same embryological origin and produce insulin, we will also discuss the possible application of gut organoids for diabetes therapy. Better understanding of the challenges associated with the current protocols for organoid culture facilitates development of scalable organoid cultures for applications in biomedicine.

Predictive capability of fasting-state glucose and insulin measurements for abnormal glucose tolerance in women with polycystic ovary syndrome

  • Chun, Sungwook
    • Clinical and Experimental Reproductive Medicine
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    • v.48 no.2
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    • pp.156-162
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    • 2021
  • Objective: The aim of the present study was to evaluate the predictive capability of fasting-state measurements of glucose and insulin levels alone for abnormal glucose tolerance in women with polycystic ovary syndrome (PCOS). Methods: In total, 153 Korean women with PCOS were included in this study. The correlations between the 2-hour postload glucose (2-hr PG) level during the 75-g oral glucose tolerance test (OGTT) and other parameters were evaluated using Pearson correlation coefficients and linear regression analysis. The predictive accuracy of fasting glucose and insulin levels and other fasting-state indices for assessing insulin sensitivity derived from glucose and insulin levels for abnormal glucose tolerance was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Significant correlations were observed between the 2-hr PG level and most fasting-state parameters in women with PCOS. However, the area under the ROC curve values for each fasting-state parameter for predicting abnormal glucose tolerance were all between 0.5 and 0.7 in the study participants, which falls into the "less accurate" category for prediction. Conclusion: Fasting-state measurements of glucose and insulin alone are not enough to predict abnormal glucose tolerance in women with PCOS. A standard OGTT is needed to screen for impaired glucose tolerance and type 2 diabetes mellitus in women with PCOS.

The Effects of Ginsenoside Re on High-Fat Diet induced Insulin Resistance in Muscle (Ginsenoside Re가 골격근의 고지방식 유도 인슐린 저항성에 미치는 영향)

  • Jung, Su-Ryun
    • Korean Journal of Exercise Nutrition
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    • v.14 no.2
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    • pp.75-80
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    • 2010
  • We evaluated the effect of the ginsenoside Re on insulin resistance of glucose transport in muscles of rats made insulin resistant with a high fat diet. After a week of adaptation period to the laboratory environment, 40 male wistar rats were randomly assigned into 2 groups (Chow diet group; CD, n = 20, High fat diet group; HFD, n = 20). After 5-week of high fat diet, Food was removed after 6:00 PM the day before the experiment. The following morning, rats were anesthetized by an intraperitoneal injection of pentobarbital sodium (50 mg/kg body wt), and the soleus muscles were removed. Before incubation, the soleus muscle was split longitudinally into strips with an average weight of 15~20 mg. After the muscle dissection was completed, the abdominal cavity was opened, and the epididymal, mesenteric, and retroperitoneal fat pads were removed and weighed. Treatment of muscles with ginsenoside Re alone had no effect on glucose transport. The high fat diet resulted in ~50% decreases glucose transport rate in soleus muscles. Treatment of muscles with ginsenoside Re in vitro for 90 min completely reversed the high fat diet-induced insulin resistance of glucose transport in soleus muscles. This effect of ginsenoside Re is specific for insulin stimulated glucose transport, as Re treatment did not reverse the high fat diet-induced resistance of skeletal muscle glucose transport to stimulation by contraction. Our results show that the ginsenoside Re induces a remarkably rapid reversal of high fat diet-induced insulin resistance of muscle glucose transport.

The Evaluation of Radioimmunoassay kits for Insulin (Insulin 측정용 방사면역측정법 시약의 평가)

  • Shin, Yong Hwan;Kim, Yun Hyun;Lee, Il Kyu;Kim, Ji Young;Seok, Jae Dong;Shin, Suk Hee
    • The Korean Journal of Nuclear Medicine Technology
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    • v.16 no.2
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    • pp.149-155
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    • 2012
  • Purpose : Serum insulin levels are useful indicator which of reflecting the function of insulin secretion in pancreatic ${\beta}$ cell and diagnosis of diabetes, differentiating the cause of impaired glucose tolerance. Insulin measurement kits have shown some differences in many ways such as test methods as well as quality control. The purpose of this study was to evaluate the diagnostic performance of seven manufacturing companies commercial kits. Materials and Methods : The values of insulin measured by three manufacturing companies (Biosource, Siemens, TFB) with 59 samples in August 2009 were compared with those measured by four manufacturing companies (Immunotech, Izotope, BNIBT, Cisbio) with 68 samples in December 2011. We evaluated precision, recovery rate, dilution test and correlation of serum insulin measurement using seven manufacturing company kits. Statistical program SPSS 12.0 was used for the verification of results. Results : The coefficients variation of the precision on all seven different kits were showed within 5.0%. Recovery rate of Biosource, Siemens, TFB kits on three different levels showed 94.2~103.7%, 99.0~104.6%, 99.7~107.6% respectively. Immunotech, Izotope, BNIBT, Cisbio were 93.5~99.1%, 91.4~99.1%, 99.2~131.0%, 84.8~102.3% respectively. There was strong correlation between the measurement of insulin by Biosource kit and that by two commercial kits, Siemens (R2=0.96), TFB (R2=0.99). There was good correlation between the measurement of insulin by TFB kit and that by three commercial kits, Immunotech (R2=0.97), Izotope (R2=0.96), Cisbio (R2=0.97). In the dilution test performed with more than 200 ${\mu}IU/ml$ high concentration samples, samples with diabetes correctly was measured in all seven manufacturing kits. However, as measured with insulinoma samples TFB, Siemens, Izotope, Cisbio kits were correctly measured, but Biosource and Immunotech kits were measured 47.4 ${\mu}IU/ml$, 72.3 ${\mu}IU/ml$, respectively. Conclusion : Serum Insulin radioimmunoassay kits were showed excellent precision, correlation and good recovery rate. However, some kits were not measured correctly in the high concentration insulin values. when selecting a kit should be considered many factors that cost effectiveness, compatible for automation equipment, high performance kit, the environment for each laboratory such as reaction time and reporting time.

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Establishment of Reference Value of Insulin Using the Statistical Analysis (통계적 분석을 통한 Insulin의 정상 참고치 설정)

  • Kim, Whe-Jung;Yoon, Pil-Young;Shin, Young-Goon;Yoo, Seon-Hee;Cho, Shee-Man
    • The Korean Journal of Nuclear Medicine Technology
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    • v.14 no.1
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    • pp.143-146
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    • 2010
  • Purpose: Insulin is involved in carbohydrate metabolism and also it's very important because it increases storage of glycogen, synthesis of fatty acids, absorption of amino acid, synthesis of protein. Insulin is clinically useful when we evaluate fasting patients in hypoglycemia, classify and predict diabetes, assess the activity of ${\beta}$-cell, research insulin resistance. We are going to increase usability of insulin assay by establishing normal reference value according to statistical analysis. Material & Method: We selected 6,648 patients who visited asan health medical center from May to August in 2008. We set exclusion criteria as family of diabetes, diabetes medication, the past history of blood glucose rise, more than 100 mg/dL in normal fasting blood glucose, outside the scope of BMI 18.5~22.9 $kg/m^2$, and more than HbA1c 6.5%. We determine whether the subgroup is portioned as sex and age or not and establish normal reference value by conducting statistical analysis as Bayesian's method and Hoffman's method. Result: Portioning of subgroup as sex and age is not needed. By statistical analysis of Bayesian method, results 1.5-11.0 uIU/mL. By statistical analysis of Hoffman method, results 1.8~12.8 uIU/mL. Conclusion: We established 1.8~12.8 uIU/mL as Insulin normal reference value by Hoffman method. This is a similar value with reporting reference value 1.7~11.8 uIU/mL in kit. This will enhance the usability of insulin assay by establishing normal reference value.

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The Association of Insulin Resistance with Cardiovascular Disease Risk and Dietary Factors in Korean Type 2 DM Patients (제2형 당뇨병 환자에서 인슐린저항성과 심혈관질환 위험요인 및 식이요인과의 관계)

  • Yu, So-Young;Hong, Hye-Sook;Lee, Hyun-Sook;Choi, Young-Ju;Huh, Kap-Bum;Kim, Wha-Young
    • Journal of Nutrition and Health
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    • v.40 no.1
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    • pp.31-40
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    • 2007
  • The purpose of this study was to investigate the association between insulin resistance and cardiovascular disease risk factors in Korean type 2 diabetes patients. The subjects were 429 (male: 218, female: 211) type 2 DM patients visited DM clinic, and they were classified into quartiles based on $K_{ITT}$ index (%/min, Insulin Tolerance Test). Anthropometric and biochemical characteristics, and dietary intakes by Food Frequency Questionnaire were assessed. The means of waist circumference, fat mass, percent body fat and abdominal fat thickness were significantly higher in the lowest quartile (the most insulin resistant group) than in the highest quartile (the least insulin resistant group) of $K_{ITT}$ index (%/min)(p<0.05), For hematological values, the lowest quartile showed significantly higher fasting blood glucose, HbA1c, C-peptide, insulin, triglyceride, ApoB/apoA-1 ratio and C-reactive protein compared to the highest quartile (p < 0.05). Moreover, $K_{ITT}$ index (%/min) was negatively correlated with waist circumference, fat mass, percent body fat, abdominal fat thickness and fasting blood concentrations of glucose, HbA1c, C-peptide, insulin, cholesterol, triglyceride, ApoB/apoA-1 ratio and C-reactive protein (p < 0.05). Nutrient intakes were not significantly different among the quartile groups of $K_{ITT}$ index (%/min) and also not correlated with insulin resistance, however, they showed correlation with obesity parameters (BMI, waist circumference, waist-hip ratio, vat mass, abdominal fat thickness), which were strongly associated with insulin resistance. In conclusion, cardiovascular disease risk would be higher as the insulin resistance grows in Korean type 2 DM patients, and nutrient intakes would affect to the insulin resistance through the effect on anthropometric parameters.

In vitro Anti-diabetic Effects of Crude Extracts of Platycodi Radix (In vitro에서 길경 추출 분획물의 항당뇨 효과 조사)

  • Ko, Byoung-Seob;Kwon, Dae-Young;Hong, Sang-Mee;Park, Sun-Min
    • Korean Journal of Food Science and Technology
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    • v.39 no.6
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    • pp.701-707
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    • 2007
  • Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.

A Study on Hypoglycemic Effects of Crude Extracts of Schizandrae Fructus (오미자 추출물의 혈당 강하 효과에 관한 연구)

  • Ko, Byoung-Seob;Park, Seong-Kyu;Choi, Soo-Bong;Jun, Dong-Wha;Choi, Mi-Kyung;Park, Sun-Min
    • Applied Biological Chemistry
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    • v.47 no.2
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    • pp.258-264
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    • 2004
  • Hypoglycemic effect of Schizandrae Fructus (SF) extract containing in Okchun-san was determined on 3T3-L1 fibroblasts and adipocytes by investigating insulin-like activity, insulin sensitizing activity and ${\alpha}-glucoamylase$ suppressing activity. SF were extracted by using 70% ethanol followed by XAD-4 column chromatography with a mixture solvent of methanol and water, and the fractional extractions were utilized for assaying hypoglycemic effect. No inhibition of ${\alpha}-glucoamylase$ activity of SF was observed. Insulin-like activity 3T3-L1 adipocytes was not shown by SF. A significant insulin sensitizing activity of SF extractions was observed in 3T3-L1 adipocytes, giving SF extractions with 1 ng/ml insulin to reach glucose uptake level increased by 50 ng/ml of insulin alone. When cells were treated with SF (Fr. 4 or 5) plus 1 ng/ml insulin, glucose uptake was increased more than seven times as compared to 1 ng/ml of insulin alone, suggesting that SF extracts increased GLUT4 content by enhancing insulin signaling. These data suggest that SF extracts (especially Fr. 4 and 5) contains an effective insulin sensitizing compounds for hypoglycemic activity in 3T3-L1 adipocytes.

Computer Simulation of Glucose-insulin Kinetics During Intravenous Glucose Tolerance Test

  • Min, B.G;Woo, E.J.
    • Journal of Biomedical Engineering Research
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    • v.4 no.1
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    • pp.9-14
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    • 1983
  • A new quantitative method was developed for separation of three interactive physiological factors (hepatic glucose balance, peripheral tissue's insulin resistivity, and insulin secretion rate) influencing glucose intolerance in diabetic mellitus using an equivalent circuit model and the intravenous glucose tolerance test (IVGTT) in six dogs and twenty two humans. The results show that the estimated model parameters of the above three factors are useful for evaluating different glucose-insulin kinetics in normal and diabetic subjects.

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Serum Insulin, Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3 Levels in Obese Adolescents (비만 청소년에서 Insulin, Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3에 대한 연구)

  • Kwon, Jung Hyun;Kim, Hyun Jin;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.48 no.11
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    • pp.1172-1178
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    • 2005
  • Purpose : Childhood Obesity is increasing throughout the world, and it is known to incur many diseases especially in later life such as diabetes and cardiovascular disorders. The purpose of this study was to investigate the association between obesity and insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3(IGFBP-3) and know if these factors are useful in predicting cardiovascular diseases. Methods : The study group consisted of 64 moderate and severe obese adolescents and the controls were normal adolescents of the same age. body mass index(BMI) was calculated by height and weight; systolic and diastolic blood pressure was measured at resting state. After 10-hour fasting period, blood cholesterol, triglyceride, high density lipoprotein(HDL) cholesterol, low density lipoprotein(LDL) cholesterol, glucose, insulin, free fatty acid, IGF-I and IGFBP-3 were measured. Results : Insulin was significantly higher in the obese adolescent group than the control group(obese group $15.6{\pm}7.0{\mu}IU/mL$, P<0.01). IGF-I was also significantly higher in the obese adolescent group than the control group(obese group $498.1{\pm}122.2ng/mL$, P<0.05). In addition, IGFBP-3 was significantly higher in the obese adolescent group than the control group(obese group $3,777{\pm}4,721ng/mL$, P<0.05). Insulin showed significantly positive correlation with BMI(r=0.3944) and obesity index(r=0.34). IGFBP-3 were significantly correlated with obesity index(r=0.419), diastolic blood pressure (r=0.264) and BMI(r=0.247). Insulin resistance index significantly positive correlation with BMI(r=0.595), blood triglycerid level(r=0.515) and obesity index(r=0.469). Conclusion : Serum insulin, insulin resistance index, IGF-I and IGFBP-3 levels may be useful to predict cardiovascular diseases in adolescent obesity.