• KSBB Journal
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• v.21 no.6 s.101
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• pp.466-473
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• 2006

Impaired insulin secretion from pancreatic beta-cells in response to glucose is an important feature in the pathology of non-insulin-dependent diabetes mellitus (NIDDM). In the course of screening for useful insulin secretagogues, we have isolated and identified YHB-2017 (Genistein) as a insulin secretion potentiator from fermentation broths of our in-house microbial library. The insulinotropic activity of YHB-2017 in isolated rat pancreatic islets was exerted only at high concentration of glucose (8.3-16 mM) but not at low concentration of glucose (3.3-5.5 mM). Also, in perifusion study with isolated rat pancreatic islets, YHB-2017 stimulated insulin secretion in a time-dependent manner when YHB-2017 was added to KRB buffer containing 16 mM glucose. In the presence of $200\;{\mu}M$ diazoxide and 35 mM KCI, which stimulates maximum $Ca^{2+}$ influx independently of KATP channel, YHB-2017 enhanced KATP channel-independent insulin secretion at high concentration glucose (16 mM). To elucidate the mechanisms of the glucose-dependent potentiation effect of YHB-2017, pharmacologic inhibitors for protein kinase A, protein kinase C and calcium/calmodulin kinase II were pre-treated and then the potentiation effect of YHB-2017 on insulin secretion was investigated. Pre-treatment of H89 as a PKA inhibitor had a significant inhibitory effect on YHB-2017-induced potentiation effect. Furthermore, western immunoblotting analyses revealed that YHB-2017 increased phosphorylation of PKA substrates and cAMP response element-binding protein (CREB) under high concentration of glucose. These results demonstrated that the insulinotropic effect of YHB-2017 is mediated through PKA signal pathway and activated amplifying $K_{ATP}$ channel-independent insulin secretion pathway.

• Journal of Life Science
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• v.27 no.3
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• pp.289-294
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• 2017

Diabetes mellitus is associated with insulin resistance, which leads to down-regulation of insulin signaling and the decreased glucose uptake. Adipocytes are sensitive to insulin, and closely implicated in insulin resistance and diabetes. Insulin stimulates differentiation of preadipocytes to adipocytes, and increases glucose transport. Allium species have been used as traditional medicine and health-promoting foods. Allium hookeri (A. hookeri) is reported to improve the pancreatic ${\beta}-cell$ damage and exhibit pancreatic anti-inflammatory activity in streptozotocin-induced diabetic rats. We investigated whether A. hookeri extract (AHE) may stimulate glucose uptake in adipocytes through increasing insulin sensitivity. AHE enhanced fat accumulation, a differentiation biomarker, under the partial induction of differentiation by insulin. $PPAR{\gamma}$, a transcription factor highly expressed in adipocytes, promotes adipocyte differentiation and insulin sensitivity. AHE increased the differentiation of preadipocytes through up-regulation of $PPAR{\gamma}$. The activation of $PPAR{\gamma}$ increases the GLUT4 expression during adipocyte differentiation. GLUT4 is responsible for glucose uptake into the adipocytes. AHE increased the expression of GLUT4 in adipocytes, and subsequently enhanced the insulin-stimulated glucose uptake. These results suggest that AHE promotes adipocyte differentiation through activation of $PPAR{\gamma}$, and leads to enhance glucose uptake in adipocytes along with GLUT4 up-regulation. Thus, AHE may be effective for the insulin-sensitizing and anti-diabetic activities.

• Journal of Animal Environmental Science
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• v.3 no.1
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• pp.1-12
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• 1997

This study was conducted to investigate the combined effects of VFA composition of rumen fluid and heat exposure (30${\pm}$2$^{\circ}C$) on the general clinical view and insulin secretory response to glucose in sheep. The total infusion of nutrients was examined in sheep via the technique of continuous alimentation. Four adult Suffolk sheep fitted with a permanent ruminal cannula and a simple T-shaped duodenal cannula were used. A peristaltic pump was used to infuse the solutions of volatile fatty acid triglycerides (VFA-TG) consisting of 70 triacetin : 20 tripropionin : 10 tributyrin (low propionin division: LP) and 50 triacetin : 40 tripropionin : 10 tributyrin (high propionin division: HP) on the basis of energy and minerals into the rumen, and casein solution into the duodenum. The effects of heat exposure and type of the levels of VFA-TG solutions on the insulin secretory response to glucose in sheep were investigated by using hyperglycemic clamp (HGC) technique. The results obtained are summarized as follows: 1. During the heat exposure (latter half of the infusion period), respiration rate, heart rate and rectal temperature increased (P＜0.01, P＜0.01, P＜0.05), but the levels of VFA-TG solutions (LP and HP division) did not affect the general clinical view except for the heart rate. 2. In the HGC technique, glucose infusion rate (GIR) and mean plasma insulin increments (MPII) tended to be ower in the heat exposure than in the thermoneutral environment, but no significant difference was found among the treatments. GIR and MPII remained unchanged between the levels of VFA-TG solutions. 3. In the HGC technique, ratio of MPII to GIR (MPII/GIR) which represents pancreatic ${\beta}$-cell response to glucose stimulation remained unchanged among the treatments.

• The Journal of Korean Medicine
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• v.31 no.4
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• pp.79-100
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• 2010

Objective: Production of ROS from glucose toxicity results in injury of pancreatic $\beta$-cells in diabetes models. This study was undertaken to examine the influence of Lespedeza Cuneata extract (LCE) on cytoprotective effects on glucose toxicity, insulin secretion and gene expression in RIN-m5F cells. Methods: First, we measured LCE's antioxidant activity by DPPH free radical-scavenging activity and SOD activity. After the various concentrations of LCE were added to the RIN-m5F cells, we measured cell viability with glucose stimulation by MTT assay and glucose-stimulated insulin secretion. We analyzed gene expression with Agilent whole mouse genome 44K oligo DNA microarray and searched for related pathways in KEGG (Kyoto Encyclopedia of Genes and Genomes). Lastly we measured INS-1, INS-2, INS-R, IRS-1, IRS-2, IRS-3, GLP-1R, and GLP-2R mRNA expression by real time RT-PCR. Results: Free radical-scavenging activity, SOD activity and insulin secretion increased dependent on LCE concentration, but LCE did not show considerable cytoprotective effect on RIN-m5F cells. More than twice expressed gene was 6362 in Oligo DNA chip. In KEGG, the most related pathway was the metabolic pathway. In the insulin signaling pathway, up expressed genes were Irs1, Mapk8, Akt1, and Lipe and down expressed genes were Rhoq, Fbp2, Prkar2b, Gck, and Prkag1. In real time RT-PCR, IRS-2, and IRS-3 expression increased significantly compared to the control group on LCE $12{\mu}g/m{\ell}$ concentration and GCK expression decreased significantly compared to the control group. Conclusions: These results show that LCE encourages insulin secretion and insulin metabolism by complicated gene mechanisms. Further mechanism study and clinical study seem to be necessary about Lespedeza Cuneata.

• Clinical and Experimental Pediatrics
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• v.61 no.7
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• pp.217-220
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• 2018

Purpose: Type 1 diabetes mellitus (T1DM) is a chronic and immune-mediated disease, which is characterized by the progressive destruction of pancreatic beta cells. T1DM precipitates in genetically susceptible individuals through environmental factors. In this study, we aimed to evaluate the impact of autoimmunity and intestinal colonization of Candida albicans on the development of T1DM. Methods: Forty-two patients newly diagnosed with T1DM and 42 healthy subjects were included in this monocentric study. The basic and clinical characteristics of the patients were recorded. T1DM-, thyroid-, and celiac-associated antibodies were evaluated. Stool cultures for C. albicans were performed to assess whether or not gut integrity was impaired in patients with T1DM. Results: The evaluation of T1DM- and thyroid-associated antibodies showed that the prevalences of islet cell antibodies and antithyroperoxidase positivity were higher in the study patients than in the patients in the control group. Furthermore, the direct examination and culture of fresh stool samples revealed that 50% of the patients with T1DM and 23.8% of the control subjects had fungi (C. albicans). Conclusion: Through this study, we suggest that the presence of intestinal C. albicans colonization at the time of the diagnosis of T1DM may indicate impairment of normal intestinal microbiota. We also suggest that there may be a tendency of T1DM in patients with a high prevalence of intestinal C. albicans.

• Nutritional Sciences
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• v.8 no.2
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• pp.111-117
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• 2005

It has been more than three decades since the first assay assessing circulating 25 (OH)D in human subjects was performed That publication as well as several that followed it defined 'normal' nutritional vitamin D status in human populations. Recently, the wisdom by which 'normal' circulating 25 (OH)D levels in human subjects were assigned in the past has come under question. It appears that sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25 (OH)D levels by plotting a Gaussian distribution is grossly inaccurate. There are many reasons why this method is inaccurate, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary recommendations for vitamin D. For instance, a 400 IU/day. AI for vitamin D is insignificant when one considers that a 10-15 minute whole body exposure to peak summer sun will generate and release up to 20,000 IU vitamin $D_3$ into the circulation. Recent studies, which orally administered up to 10,000 IU/day vitamin $D_3$ to human subjects for several months, have successfully elevated circulating 25 (OH)D levels to those observed in individuals from sun-rich environments. Further, we are now able to accurately assess sufficient circulating 25 (OH)D levels utilizing specific biomarkers instead of guessing what an adequate level is. These biomarkers include intact parathyroid hormone (PTH), calcium absorption, bone mineral density (BMD), insulin resistance and pancreatic beta cell function. Using the data from these biomarkers, vitamin D deficiency should be defined as circulating levels of 25 (OH)D$\leq$30 ng/mL. In certain cases, such as pregnancy and lactation, significantly higher circulating 25 (OH)D levels would almost certainly be beneficial to both the mother and recipient fetus/infant.

• Proceedings of the Korean Nutrition Society Conference
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• 2004.11a
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• pp.22-33
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• 2004

It has been more than three decades since the first assay assessing circulating 25(OH)D in human subjects was performed. That publication as well as several that followed it defined 'normal' nutritional vitamin D status in human populations. Recently, the wisdom by which 'normal' circulating 25(OH)D levels in human subjects were assigned in the past has come under question. It appears that sampling human subjects, who appear to be free from disease, and assessing 'normal' circulating 25(OH)D levels by plotting a Gaussian distribution is grossly inaccurate. There are many reasons why this method is inaccurate, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary recommendations for vitamin D. For instance, a 400IU/day. AI for vitamin D is insignificant when one considers that a 10-15 minute whole body exposure to peak summer sun will generate and release up to 20,000 IU vitamin $D_3$ into the circulation. Recent studies, which orally administered up to 10,000 IU/day vitamin $D_3$ to human subjects for several months, have successfully elevated circulating 25(OH)D levels to those observed in individuals from sun-rich environments. Further, we are now able to accurately assess sufficient circulating 25(OH)D levels utilizing specific biomarkers instead of guessing what an adequate level is. These biomarkers include intact parathyroid hormone (PTH), calcium absorption, bone mineral density (BMD), insulin resistance and pancreatic beta cell function. Using the data from these biomarkers, vitamin D deficiency should be defined as circulating levels of $25(OH)D{\leq}30ng/mL$. In certain cases, such as pregnancy and lactation, significantly higher circulating 25(OH)D levels would almost certainly be beneficial to both the mother and recipient fetus/infant.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.389-397
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• 2011

This study tried to integrate the traditional oriental medical theories and results of experimental studies of herbaceous plants on anti-diabetes. And I tried to analyze recent experimental study trend on the anti-diabetic herb. I searched anti-diabetic herb studies on 4 korean databases and 10 korean journals by keywords, 'diabetes', 'blood glucose', 'glycometabolism', 'pancreatic ${\beta}$-cell', etc. In order to see detail review, searching was performed from 2000 to 2010. And I searched 125 study cases concerning anti-diabetic herb and 72 varieties herbaceous plants used in study of anti-diabetes. and I analyzed the choice motives of each herb for anti-diabetic study, the extract methods and anti-diabetic evaluation contents. And I analyzed anti-diabetic herbs from a traditional oriental medical point of view. When the researchers chose herb for anti-diabetic experiment, just 8.8% of the choice was based on the oriental medical evidences. I found that 60.6% of the herb shown to be effective in diabetes experimentally had oriental medical theory-based Properties(性). There were studies with whole plants(16.8%), aqueous extract(45.6%), methanol extract(8.0%), ethanol extract(8.0%) and comparative studies of more than 2 types of extracts or various fractions(18.4%). The most frequent experimental diabetic models was diabetic mouse induced by streptozotocin(STZ)(87.8%). And there were db/db mouse(6.7%), ob/ob mouse(1.1%), etc. 33.6% of all studies just measured hematological indices of diabetes, and 66.4% researches analyzed details. To improve herbaceous plants study on diabetes, we oriental medical scientists have to integrate the oriental medical theories and results of experimental studies.

• YAKHAK HOEJI
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• v.55 no.4
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• pp.301-308
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• 2011

Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

• Journal of Pharmacopuncture
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• v.20 no.4
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• pp.235-242
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• 2017

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane-spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic ${\beta}$ cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.