• Korean Journal of Pharmacognosy
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• v.33 no.1 s.128
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• pp.21-28
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• 2002

Antidiabetic effects of the acid hydrolysate of silk fibroin were investigated by oral administration to animal models for diabetes mellitus, Fibroin protein was extracted from cocoon and digested to peptides of low-molecular weight range (mainly below 3,000) and amino acids by acid hydrolysis, Feeding of the fibroin hydrolysate resulted in a significant recovering effect on reduction of body weight gain and a lowering effect on blood glucose gain in streptozotocin-induced diabetic Sprague Dawley rats (STZ rats) which were used as an insulin-dependent diabetic animal model. But the body weight and blood glucose level in C57BL/KsJ-db/db mice (db/db mice), an non-insulin-dependent diabetic animal model, were not changed significantly by the feeding, On the other hand, plasma leptin levels increased according to increased feeding amount of the hydrolysate in STZ rats and db/db mice in common, It was concluded from the results that the fibroin hydrolysate might stimulate the insulin secretion by recovering or activating pancreatic ${\beta}$ cells and result in the increased plasma leptin level. It was also deduced that the antidiabetic improvements in body weight and blood glucose gain in STZ were thought to be due to the increased insulin secretion, but in db/db mice of which the diabetic symptoms were caused by insulin resistance, the stimulated secretion of insulin was unlikely to be able to change body weight and blood glucose level significantly.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.201-209
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• 2018

G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

• CELLMED
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• v.7 no.1
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• pp.1.1-1.10
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• 2017

Minerals are individual of the components of foods and are not produced in the body but essential for best possible health. Several essential metals are vital for the appropriate performance of various enzymes, transcriptional factors and proteins that are essential in various biochemical paths. Metals like zinc (Zn), magnesium (Mg), and manganese (Mn) are cofactors of hundreds of enzymes. Zn is involved in the synthesis and secretion of insulin from the pancreatic ${\beta}-cells$. Chromium (Cr) increases the insulin receptors activity on target tissues, mainly in muscle cells. Insulin hormone is required to maintain the blood glucose amount in normal range. Continual increase of blood serum glucose level leads to marked chronic hyperglycemia or diabetes mellitus. Deficiency of insulin or its resistance, blood glucose level exceeds the upper limit of the common range of 126 mg/dl. Poor glucose control and diabetes changes the levels of essential trace elements such as Zn, Mg, Mn, Cr, iron etc. by rising urinary excretion and their related decrease in the blood. The aim of this article to discusses the important roles of essential trace elements in particular perspective of type 2 diabetes.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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• pp.25-31
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• 2000

ATP-sensitive potassium channels ($K_{ATP}$ channels) play an important role in insulin secretion from pancreatic beta cells. We have investigated the effect of propofol on $K_{ATP}$ channels in cultured single pancreatic beta cells of rats. Channel activity was recorded from membrane patches using the patch-clamp technique. In the inside-out configuration bath-applied propofol inhibited the $K_{ATP}$ channel activities in a dose-dependent manner. The half-maximal inhibition dose (ED50) was $48.6{\pm}8.4\;{\mu}M$ and the Hill coefficient was $0.73{\pm}0.11.$ Single channel conductance calculated from the slope of the relationship between single channel current and pipette potential $(+20{\sim}+100\;mV)$ was not significantly altered by propofol $(control:\;60.0{\pm}2.7\;pS,\;0.1\;mM\;propofol:\;58.7{\pm}3.5\;pS).$ However, mean closed time was surely increased. Above results indicate that propofol blocks the $K_{ATP}$ channels in the pancreatic beta cells in the range of its blood concentrations during anesthesia, suggesting a possible effect on insulin secretion and blood glucose level.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.340-345
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• 2008

Extract of Acanthopanax senticosus has recently been demonstrated to possess significant antidiabetic potential, in accordance with the traditional use of this plant as an antidiabetic natural health product. The present study evaluated the effects of fermented extract (FE) of this plant on glucose-stimulated insulin secretion, glucose uptake, and streptozotocin-induced type 1 diabetes model. A 3 h pretreatment with FE prevented $IL-1{\beta}$ and $IFN-{\gamma}$ toxicity in isolated rat islets. However, it did not affect insulin-stimulated glucose uptake in C2C12 myotubes. In addition, pretreatment of mice with FE blocked the destruction of streptozotocin-induced islets and the development of type 1 diabetes. FE reduced blood glucose level, increased insulin secretion, and improved glucose tolerance in streptozotocin-treated mice, whereas nonfermented extract (NFE) had moderate effects. Immunohistochemical staining for insulin clearly showed that pretreatment with FE blocked the STZ-induced islets destruction and restored the number of islet cells that secreted insulin to the level of the control. Although the active principles and their mechanisms of action remain to be identified, FE may nevertheless represent a novel complementary therapy and a source of novel therapeutic agents against type 1 diabetes mellitus.

• 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.

• Journal of Nutrition and Health
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• v.34 no.5
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• pp.485-492
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• 2001

The prevalence of type 2 diabetes mellitus has been rapidly increased in parallel with the westernization of eating behavior in Korea. Increased consumption of animal fat and simple sugar can be potential contributors for insulin resistance. The purpose of the study was to determine whether Western-(WD) and Korean-style(KD) diets altered insulin secretion and insulin resistance in male Sprague Dawley rats. Rats weighing 98$\pm$5g were provided by KD(77 En% of starch, 5 En% of corn oil and 13 En% of gluten plus 5 En% of casein), WD(42 En% of starch, 40 En% of butter and 18% of casein) or control diet(62 En% of starch, 20 En% of corn oil and 18% of casein) for 12 weeks. Body weights were lower in KD compared to WD. Fasting blood glucose levels were not different among diets. Insulin secretion from the beta cells was higher by 2.2$\pm$0.4 folds in WD than KD at baseline. In hyperglycemic clamp insulin secretion was higher in WD than KD and CD. Whole body glucose disposal rates referred to the state of insulin sensitivity were lowest in WD among groups. Glycogen deposits in soleus and quadriceps muscles were lowest in WD among all groups, but their triglyceride contents were highest. GLUT4 contents and glycogen synthase were lowest in WD in both muscles. In conclusions, westernization of diets needed more insulin to normalization of blood glucose levels due to increased insulin resistance. Thus, WD would lead to increased prevalence of diabetes mellitus when increased insulin resistance could not be compensated by insulin secretion in the case of elevated blood glucose levels. (Korean J Nutriton 34(5) : 485~492, 2001)

• Genomics & Informatics
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• v.12 no.4
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• pp.240-246
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• 2014

Mutation in HNF1B, the hepatocyte nuclear factor-$1{\beta}$ (HNF-$1{\beta}$) gene, results in maturity-onset diabetes of the young (MODY) 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-$1{\beta}$ in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain) mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2). The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05). Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic ${\beta}$-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05). However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in ${\beta}$-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.141-149
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• 2015

"G protein-coupled receptor 40" (GPR40), a receptor for long-chain fatty acids, mediates the stimulation of glucose-induced insulin secretion. We examined the profiles of differential gene expression in GPR40-activated cells treated with linoleic acid, and finally predicted the integral pathways of the cellular mechanism of GPR40-mediated insulinotropic effects. After constructing a GPR40-overexpressing stable cell line (RIN-40) from the rat pancreatic ${\beta}$-cell line RIN-5f, we determined the gene expression profiles of RIN-5f and RIN-40. In total, 1004 genes, the expression of which was altered at least twofold, were selected in RIN-5f versus RIN-40. Moreover, the differential genetic profiles were investigated in RIN-40 cells treated with $30{\mu}M$ linoleic acid, which resulted in selection of 93 genes in RIN-40 versus RIN-40 treated with linoleic acid. Based on the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG, http://www.genome.jp/kegg/), sets of genes induced differentially by treatment with linoleic acid in RIN-40 cells were found to be related to mitogen-activated protein (MAP) kinase- and neuroactive ligand-receptor interaction pathways. A gene ontology (GO) study revealed that more than 30% of the genes were associated with signal transduction and cell proliferation. Thus, this study elucidated a gene expression pattern relevant to the signal pathways that are regulated by GPR40 activation during the acute period. Together, these findings increase our mechanistic understanding of endogenous molecules associated with GPR40 function, and provide information useful for identification of a target for the management of type 2 diabetes mellitus.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.304-312
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• 2018

Regulatory T cells (Treg), known as immune-suppressors, may help modulate the immune response. In this study, we investigated the effect of Treg-derived $TGF-{\beta}1$ on pancreatic islet cell function in vitro and in vivo. One hundred eighty IEQ (islet equivalents) of pancreatic islets, the marginal amount to regulate blood glucose level after syngeneic islet transplantation in mouse type 1 diabetes (T1D) model, were co-cultured with $4{\times}10^6$ Treg cells for 48 hours. The changes in $TGF-{\beta}1$, interleukin-6 (IL-6), and insulin secretion levels were measured and analyzed among the Treg-only group, the islet-only group, and the Treg/islet co-cultured group. In the Treg/islet co-cultured group, IL-6 and insulin secretion levels were increased (P<0.0005, P<0.005) and islet viability was improved (P<0.005) compared with the islet-only group. Furthermore, after transplantation, the co-cultured islets regulated blood glucose levels efficiently in the T1D mouse model. These data suggest that Treg could improve islet functions and viability via the $TGF-{\beta}1$ secretion pathway (P<0.05~0.005), thus the use of Treg in islet transplantation should be explored further.