• 한방안이비인후피부과학회지
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• 제20권1호통권32호
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• pp.154-168
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• 2007

Objective : The present study was carried out to investigate the preventive effect of Agrimonia pilosa Ledebour on Streptozotocin(STZ)-induced Diabetes mellitus. Method : Agrimonia pilosa Ledebour was given to rats with oral administration. The experimental animals were divided into 3groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with Agrimonia pilosa Ledebour. The effect of Agrimonia pilosa Ledebour on STZ-induced diabetes was observed by measuring the survival rate of rats, weight of rats, FER, blood glucose, each organ weight of rat, total cholesterol, HDL, GOT, GPT & creatinine. Result : STZ caused hyperglycemia and hypoinsulinemia by a selectively destroying pancreatic ${\beta}-cell$. Agrimonia pilosa Ledebour treatment don't protected them from hyperglycemia and hypoinsulinemia. Organ weight only liver weight decreased but kidney, heart & spleen shows no significant changes. Agrimonia pilosa Ledebour significantly don't recoverd the increase of several biochemical parameters such as blood glucose, total cholesterol, HDL, GOT, GPT & creatinine is vice versa. Conclusion : Agrimonia pilosa Ledebour extract group did not show significant difference compared with STZ-induced Diabetes Mellitus group.

• Annals of Pediatric Endocrinology and Metabolism
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• 제22권1호
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• pp.15-26
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• 2017

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with T2D suffer from various diabetes-related complications. Since there are many patients with T2D that cannot be controlled by previously developed drugs, it has been necessary to develop new drugs, one of which is a glucagon-like peptide-1 (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related conditions by augmenting pancreatic ${\beta}-cell$ insulin secretion and having the low risk of causing hypoglycemia. Because of a very short half-life of GLP-1, many researches have been focused on the development of GLP-1 receptor (GLP-1R) agonists with long half-lives such as exenatide and dulaglutide. Now GLP-1R agonists have a variety of dosing-cycle forms to meet the needs of various patients. In this article, we review the physiological features of GLP-1, the effects of GLP-1 on T2D, the features of several GLP-1R agonists, and the therapeutic effect on T2D.

• Journal of Obesity & Metabolic Syndrome
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• 제27권4호
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• pp.213-222
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• 2018

Bariatric surgery has evolved from a surgical measure for treating morbid obesity to an epochal remedy for treating metabolic syndrome as a whole, which is represented by type 2 diabetes mellitus. Numerous clinical trials have advocated bariatric or metabolic surgery over nonsurgical interventions because of markedly superior metabolic outcomes in morbidly obese patients who satisfy traditional criteria for bariatric surgery (body mass index [BMI] >$35kg/m^2$) and in less obese or simply overweight patients. Nevertheless, not all diabetes patients achieve the most desirable outcomes; i.e., diabetes remission after metabolic surgery. Thus, candidates for metabolic surgery should be carefully selected based on comprehensive preoperative assessments of the risk-benefit ratio. Predictors for diabetes remission after metabolic surgery may be classified into two groups based on mechanism of action. The first is indices for preserved pancreatic beta-cell function, including younger age, shorter duration of diabetes, and higher C-peptide level. The second is the potential for an insulin resistance reduction, including higher baseline BMI and visceral fat area. Several prediction models for diabetes remission have been suggested by merging these two to guide the joint decision-making process between clinicians and patients. Three such models, DiaRem, ABCD, and individualized metabolic surgery scores, provide an intuitive scoring system and have been validated in an independent external cohort and can be utilized in routine clinical practice. These prediction models need further validation in various ethnicities to ensure universal applicability.

• BMB Reports
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• 제54권9호
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• pp.451-457
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• 2021

Over the last decades, research has focused on the role of pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPPs) in regulating cellular signaling via PI3K/Akt inhibition. The PKB/Akt signaling imbalances are associated with a variety of illnesses, including various types of cancer, inflammatory response, insulin resistance, and diabetes, demonstrating the relevance of PHLPPs in the prevention of diseases. Furthermore, identification of novel substrates of PHLPPs unveils their role as a critical mediator in various cellular processes. Recently, researchers have explored the increasing complexity of signaling networks involving PHLPPs whereby relevant information of PHLPPs in metabolic diseases was obtained. In this review, we discuss the current knowledge of PHLPPs on the well-known substrates and metabolic regulation, especially in liver, pancreatic beta cell, adipose tissue, and skeletal muscle in relation with the stated diseases. Understanding the context-dependent functions of PHLPPs can lead to a promising treatment strategy for several kinds of metabolic diseases.

• 생약학회지
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• 제52권2호
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• pp.77-83
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• 2021

The number of people suffering from diabetes have been increased around the world. In this study, we investigated the antidiabetic and antioxidant effects of Anthriscus sylvestris(L.) Hoffm and its main compounds. It was divided into root(R) and aerial part(AP) for comparative analysis. Total polyphenol, total flavonoid content was higher in AP extract, but nodakenin content was higher in R(1169.13 ± 6.00 mg/g) extract. Antioxidant activity was also higher in AP extract. To compare antidiabetic efficacy, we analyzed the effects of R and AP extracts on ɑ-glucosidase inhibition(AGI), dipeptidyl peptidase-4(DPP-4) and protein tyrosine phosphatase(PTP)1B activity. R and AP extracts showed similar effects on AGI and DPP-4 activity in a concentration dependent manner, and there was no effect on PTP1B activation. Glucose uptake(139.51 ± 3.19%) in 3T3-L1 cells was more effective in the AP extract-treated group than the positive control, rosiglitazone, group. Both R and AP extracts were effective in protecting against pancreatic beta cell damage caused by hyperglycemia. These results suggest that Anthriscus sylvestris(L.) Hoffm. could be used as a candidate for diabetes treatment.

• Genomics & Informatics
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• 제12권4호
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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.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.100-105
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• 2008

The sphingolipid metabolites act as lipid mediator for cell proliferation and apoptosis in mammalian cells. In bacteria, sphingolipid metabolism remains unknown. The purpose of this study was to investigate whether sphingolipid metabolism is potential target for fumonisin $B_1$($FB_1$) and desipramine in Sphingomonas chungbukensis, Gram-negative bacteria, by comparing the intracellular contents of bacterial sphingolipids with ones of HIT-T15 ${\beta}$-cells, hamster pancreatic cells. The concentrations of ceramide and dihydroceramide were 18.0 ${\pm}$ 12.0 and 0.025 ${\pm}$ 0.018 nmol/mg protein, respectively, in HIT-T15 cells. However, the concentrations of ceramide and dihydroceramide in the bacterial culture were 2.0 ${\pm}$ 1.2 and 10.6 ${\pm}$ 5.5 nmol/mg protein, respectively. $FB_1$ decreased the level of ceramide from 18.0 to 3.8 nmol/mg protein in HIT-T15 ${\beta}$-cells. However, dihydroceramide content in $FB_1$-treated HIT-T15 cells was slightly decreased compared with the control culture. When S. chungbukensis was treated with either $FB_1$ or desipramine, dihydroceramide level was increased by 5- and 4-fold, respectively, compared with the control bacteria. These results indicate that $FB_1$ and desipramine may act as an activator in bacterial sphingolipid biosynthetic pathway, and bacterial sphingolipid metabolism pathway appears to be different from the pathway of mammalian cells.

• Preventive Nutrition and Food Science
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• 제20권2호
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• pp.94-101
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• 2015

Grape products have been known to exert greater antioxidant and anti-obesity than anti-hyperglycemic effects in animals and humans. Omija is used as an ingredient in traditional medicine, and it is known to have an anti-hyperglycemic effect. We investigated whether the combined extracts of grape pomace and omija fruit (GE+OE) could reduce fat accumulation in adipose and hepatic tissues and provide beneficial effects against hyperglycemia and insulin resistance in type 2 diabetic mice. C57BL/KsJ-db/db mice were fed either a normal control diet or GE+OE (0.5% grape pomace extract and 0.05% omija fruit extract, w/w) for 7 weeks. GE+OE decreased plasma leptin and resistin levels while increasing adiponectin levels and reducing the total white adipose tissue weight. Furthermore, GE+OE lowered plasma free fatty acid (FFA), triglyceride, and total-cholesterol levels as well as hepatic FFA and cholesterol levels. Hepatic fatty acid synthase and glucose 6-phosphate dehydrogenase activities were decreased in the GE+OE group, whereas hepatic ${\beta}$-oxidation activity was increased. Furthermore, GE+OE supplementation not only reduced hyperglycemia and pancreatic ${\beta}$-cell failure but also lowered blood glycosylated hemoglobin and plasma insulin levels. The homeostasis model assessment of insulin resistance levels was also decreased and the decrease seems to be mediated by the lowered activities of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinases. The present data suggest that GE+OE may have the potential to reduce hyperglycemia, insulin resistance, and obesity in patients with type 2 diabetes.

• Biomolecules & Therapeutics
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• 제26권2호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제12권2호
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• pp.83-87
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• 2008

The fyn-related kinase (FRK) belongs to the tyrosine kinase family of protein kinases. Recent studies have shown that Frk affects pancreatic beta cell number during embryogenesis and promotes beta cell cytotoxic signals in response to streptozotocin. To investigate the genetic association between FRK polymorphisms and the risk of obesity in Korean population, single nucleotide polymorphisms (SNPs) in the FRK gene region were selected and analyzed. The body mass index (BMI) was calculated, and biochemical data (systolic blood pressure, diastolic blood pressure, hemoglobin A1C, triglyceride, total cholesterol, high density lipoprotein, and low density lipoprotein) of blood sample from each subject were also measured. One hundred fifty five healthy control and 204 overweight/obesity subjects were recruited. Genotype frequencies of six SNPs [rs6568920 (+8391G>A), rs3756772 (+56780A>G), rs3798234 (+75687C>T), rs9384970 (+68506G>A), rs1933739 (+72978G>A), and rs9400883 (+75809A>G)] in the FRK gene were determined by Affymetrix Targeted Genotyping Chip data. According to the classification of Korean Society for the Study of Obesity, control (BMI 18 to < 23) and overweight/obesity (BMI$\geq$23) subjects were recruited. For the analysis of genetic data, EM algorithm, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used. Multiple logistic regression analysis (codominant, dominant, and recessive models) was performed. Age and gender as covariates were adjusted. For biochemical data, Student's t test was used. The mean value of BMI in the control and overweigh/obesity groups was 21.1${\pm}$1.2 (mean${\pm}$SD) and 25.6${\pm}$2.0, respectively. All biochemical data of the overweight/obesity group were statistically significance, compared with the control group. Among six SNPs, two linkage disequilibrium (LD) blocks were discovered. One block consisted of rs1933739 and rs9400883, and the other comprised rs3756772 and rs3798234. One SNP (rs9384970, +68506G>A) showed an association with overweight/obesity in the codominant model (p=0.03). Interestingly, the AA genotype distribution in the overweight/obesity group (n=7, 3.5%) was higher than those in the control group (n=1, 0.6%), which is not found in either Japanese or Chinese subjects. Therefore, the AA genotype of rs9384970 may be a risk factor for development of obesity in Korean population. The results suggest that FRK may be associated with overweight/obesity in Korean population.