• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.25-39
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• 2010

Background : At high glucose levels in $\beta$-cells, cell viability and insulin secretion are decreased by glucotoxicity. Sopyung-tang(SPT) had an effect on blood glucose level decrease and antioxidant enzyme activities in streptozotocin-induced diabetic rats. Objectives : This study performed a series of experiment to verify the effects of SPT extract on the cell viability, antioxidant enzyme activities, insulin secretion and insulin mRNA expression at hyperglycemic states of RIN-m5F. Methods : After treatment at various concentrations of SPT added to the RIN-m5F cells, cell viability by MTT assay, free radical-scavenging activity, SOD activity and insulin secretion were measured. Additionally, insulin-related gene expression was measured using real-time RT-PCR. Results : Compared to the control group, SPT extract showed considerable effects on RIN-m5F cell viability, DPPH radical-scavenging activity, superoxide dismutase (SOD) activity, insulin secretion and insulin-related gene expression. Conclusions : This study showed that SPT extract has an effect on $\beta$-cell cell viability, insulin secretion and insulin-related gene expression. Thus, SPT extract may be used for treatment of diabetes and its complications. Further mechanism studies of SPT seem to be necessary on the glucotoxicity and oxidative stress.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.361-370
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• 2004

The discovery of insulin receptor substrate (IRS) proteins and their role to link cell surface receptors to the intracellular signaling cascades is a key step to understanding insulin and insulin-like growth factor (IGF) action. Moreover, IRS-proteins coordinate signals from the insulin and IGF receptor tyrosine kinases with those generated by proinflammatory cytokines and nutrients. The IRS2-branch of the insulin/IGF signaling cascade has an important role in both peripheral insulin response and pancreatic $\beta$-cell growth and function. Dysregulation of IRS2 signaling in mice causes the failure of compensatory hyperinsulinemia during peripheral insulin resistance. IRS protein signaling is down regulated by serine phosphorylation or protea-some-mediated degradation, which might be an important mechanism of insulin resistance during acute injury and infection, or chronic stress associated with aging or obesity. Under-standing the regulation and signaling by IRS1 and IRS2 in cell growth, metabolism and survival will reveal new strategies to prevent or cure diabetes and other metabolic diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.2
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• pp.186-193
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• 2007

The prevalence of diabetes has increased to 8% of population. Unlike type 2 diabetes in the western countries, Korean diabetic patients are nonobese and have low serum insulin levels. As the increased prevalence of diabetes and the peculiar characteristics may be related to dietary fat contents, we determined their effects on insulin resistance, insulin secretion and pancreatic $\beta-cell$ mass in 90% pancreatectomized (Px) diabetic rats in the present study. The rats were provided with low fat diet (LF, 10 energy% fat), moderate fat diet (MF, 25 energy% fat) and high fat diet (HF, 40 energy% fat) for 6 months. HF increased body weight and epidydimal fat pads parallel with increased food intake compared to LF and MF. Fasting serum glucose and insulin levels and homeostasis model assessment of insulin resistance were higher in HF, compared to LF and MF, indicating that HF increased insulin resistance. Rats fed LF and MF diets reduced insulin resistance, but only rats fed MF improved pancreatic $\beta-cell$ mass and insulin secretion capacity, measured by hyperglycemic clamp and in situ pancreatic perfusion. LF had low insulin secretion capacity and pancreatic $\beta-cell$ mass, indicating the increased possibility of diabetic prevalence and progression. MF increased $\beta-cell$ mass by stimulating $\beta-cell$ proliferation and neogenesis and reducing $\beta-cell$ apoptosis. In conclusion, MF is effective for the prevention of prevalence and progression of diabetes.

• Korean Journal of Clinical Laboratory Science
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• v.45 no.4
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• pp.131-138
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• 2013

Insulin resistance and pancreatic beta cell dysfunction have been established as being related to the diabetes. Lately, what is emphasizing is that those have been shown as something related to the metabolic syndrome and cardiovascular disease. Homeostasis model assessment (HOMA), simple index is calculated on blood levels of fasting glucose and insulin. And HOMA has been widely validated and applied for insulin resistance and pancreatic beta cell dysfunction. We also assessed the factors relative to insulin resistance and ${\beta}$ cell function determined by HOMA. The data from the 2010 Korean National Health and Nutrition Examination Survey were used. Analysis was done for 3,465 nondiabetic subjects (male 1,357, female 2,108). At baseline, anthropometric measurements were done and fasting glucose, insulin, lipid (Total cholesterol, HDL cholesterol, LDL cholesterol and Triglycerides) profiles were measured. HOMA-insulin resistance (HOMA-IR) and beta cell function (HOMA ${\beta}$-cell) were calculated from fasting glucose and insulin levels. In male, the value of HOMA-IR and HOMA ${\beta}$-cell was the highest among 30's and decreased as the age increased. In female, the value of HOMA-IR increased with age, while HOMA ${\beta}$-cell decreased. High HOMA-IR and low HOMA ${\beta}$-cell were associated with the highest value of fasting glucose and systolic blood pressure. Low HOMA-IR and high HOMA ${\beta}$-cell showed the lowest concentration of fasting glucose and the highest concentration of HDL cholesterol. High HOMA-IR and high HOMA ${\beta}$-cell were connected with BMI, Total cholesterol, LDL cholesterol, and Triglycerides. There was a negative correlation between HOMA ${\beta}$-cell and age. The correlation coefficients of HOMA-IR and HOMA ${\beta}$-cell showed the highest value among weight, BMI and WC.

• Asian-Australasian Journal of Animal Sciences
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• v.10 no.2
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• pp.233-239
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• 1997

A mammary epithelial cell line (MAC-T) established as a model for lactation was utilized to identify and characterize effects of various hormones upon insulin-like growth factor binding protein secretion. Ligand and immunoblot analyses of conditioned media indicated that insulin-like growth factor binding protein-2 was secreted by MAC-T cells. Insulin-like growth factor-I stimulated insulin-like growth factor binding protein-2 secretion in a dose-dependent manner, but prolactin and bovine somatotropin did not alter insulin-like growth factor binding protein-2 secretion. Insulin increased and cortisol decreased insulin-like growth factor binding protein-2 secretion. Effects of insulin-like growth factor-I on insulin-like growth factor binding protein-2 secretion support previous studies using primary cultures of bovine mammary cells and bovine fibroblasts. Effects of cortisol and insulin on insulin-like growth factor binding protein-2 secretion may be explained by changes in protein synthesis. In addition, supraphysiological doses of insulin can cross-react with the insulin-like growth factor-I receptor and stimulate insulin-like growth factor binding protein-2 secretion. MAC-T cells provide a model system to study mechanisms that regulate local insulin-like growth factor-I bioactivity.

• 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.

• Biomedical Science Letters
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• v.18 no.3
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• pp.193-200
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• 2012

We examined the effects of polyamines such as putrescine and cadaverine on the biosynthesis and secretion of insulin in the mouse pancreatic ${\beta}$-cell line, MIN-6. Basal insulin secretion (BIS) and glucose-stimulated insulin secretion (GSIS) from the MIN-6 cells were significantly increased by 20 min- or 24 h-treatment with micromolar concentrations of polyamines. To determine whether the enhancement was due to increase of insulin production by polyamines, we investigated the insulin mRNA and protein production. Both insulin mRNA and protein production were found to be not significantly affected by the polyamine treatment. Next, we examined the expression of several transcription factors (TFs) related to insulin synthesis and secretion in order to identify upstream events responsible for the promotion of insulin secretion of MIN6 cells by polyamines. Of the 6 TFs tested, MafA was induced by treatment of polyamines. MafA mRNA and protein expressions increased with treatment of polyamines. Overall results suggest that cadaverine and putrescine promote the insulin secretion process rather than the insulin biosynthesis from MIN6 cells. Also MafA may be involved in the enhanced insulin secretion process. Further studies are needed to elucidate the underlying mechanisms for promotion of insulin secretion by polyamines.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.469-475
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• 2014

BACKGROUND/OBJECTIVE: The goal of the present study was to investigate the effects of moderate caloric restriction on ${\beta}$-cell function and insulin sensitivity in middle-aged obese Korean women. SUBJECTS/METHODS: Fifty-seven obese pre-menopausal Korean women participated in a 12-week calorie restriction program. Data on total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and fasting serum levels of glucose, insulin, C-peptide, blood pressure, leptin and anthropometrics were collected. A dietary intake assessment was based on three days of food recording. Additionally, ${\beta}$-cell function [homeostasis model assessment of ${\beta}$-cell (HOMA-${\beta}$), insulinogenic index (ISI), C-peptide:glucose ratio, and area under curve insulin/glucose ($AUC_{ins/glu}$)] and insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR), Quantitative insulin-sensitivity check index (QUICKI) and Matsuda index (MI)] were recorded. RESULTS: When calories were reduced by an average of 422 kcal/day for 12 weeks, BMI (-2.7%), body fat mass (-10.2%), and waist circumference (-5%) all decreased significantly (P < 0.05). After calorie restriction, weight, body fat percentage, hip circumference, BP, TC, HDL-C, LDL-C, plasma glucose at fasting, insulin at fasting and 120 min, $AUC_{glu}$ and the insulin area under the curve all decreased significantly (all P < 0.05), while insulin sensitivity (HOMA-IR, QUICKI and Matsuda index) measured by OGTT improved significantly (P < 0.01). CONCLUSIONS: Moderate weight loss due to caloric restriction with reduction in insulin resistance improves glucose tolerance and insulin sensitivity in middle-aged obese women and thereby may help prevent the development of type 2 diabetes mellitus.

• The Journal of Korean Medicine
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• v.25 no.4
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• pp.200-208
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• 2004

Objective: Non-insulin Dependent Diabetes Mellitus (NIDDM) is characterized by insulin resistance, which affects the glucose transportation inside the cell. The purpose of this study was to find out how Palmijihwangtang (PMT) and exercise influence the glucose transport metabolism in the organ muscles of ZDF (zucker diabetic fatty) rat with insulin resistance. Methods: Using three male normal zucker rats and twelve male obese rats, they were divided into a normal lean group (N=3), obese control group (N=3), obese exercises group (N=3), obese medication group (N=3), obese exercise and medication group (N=3). Treadmill exercise were repeated with 27m/min speed for an hour a day, five days a week, for 8 weeks. And 20β/sub ￠/ of PMT was orally administered twice a day for 8 weeks, after that a period blood sample was exsanguinated by heart perforation and was analyzed. Results: The body weight of the OM and OEM group showed a significant decrease among all the obese groups. The blood insulin level increased significantly of all groups in comparison with the N group. All of the OE, OM and the OEM groups showed a significant decrease of insulin level compared with the OC group; especially the OEM group demonstrated the most among obese groups. Regarding GLUT-4 level, OEM was the unique group showed a significant increase among all the obese groups. The VAMP-2 level in myocardium cell membrane was increased significantly at OC group in comparison with the N group, whereas the OEM group only showed significant decrease of it. In addition, the VAMP-2 level in pancreas β-cell was significantly decreased at all the obese groups in comparison with the N group. Only the OEM group showed significant increase among all the obese groups. Conclusion: Palmijihwangtang (PMT) and exercise could effectively promote the insulin metabolism in pancreas β-cells and activate the glucose transport process in myocardium cell membrane by lowering the insulin resistance of ZDF rats.

• Molecules and Cells
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• v.40 no.5
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• pp.371-377
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• 2017

Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time- and dose-dependent manners and insulin receptor shRNA completely abolished RANK expression induced by insulin in bone marrow-derived monocyte/macrophage cells (BMMs). Moreover, the addition of insulin in the presence of RANKL promoted RANK expression. The ability of insulin to regulate RANK expression depends on extracellular signal-regulated kinase 1/2 (ERK1/2) since only PD98059, an ERK1/2 inhibitor, specifically inhibited its expression by insulin. However, the RANK expression by RANKL was blocked by all three mitogen-activated protein (MAP) kinases inhibitors. The activation of RANK increased differentiation of BMMs into tartrate-resistant acid phosphatase-positive ($TRAP^+$) osteoclasts as well as the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of vacuolar ($H^+$) ATPase (v-ATPase) Vo domain (Atp6v0d2), genes critical for osteoclastic cell-cell fusion. Collectively, these results suggest that insulin induces RANK expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation.