• 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.

• Journal of Life Science
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• v.20 no.7
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• pp.1113-1120
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• 2010

This study investigated the efficacy of macelignan and hot water with Chinese traditional herb (CTH) extract on altering severe diabetic conditions in C57BL/KsJ-db/db mice. Previously, the anti-diabetic effects of macelignan were partly reported as a PPAR $\alpha/\gamma$-dual agonist. Here, we futher studied whether a combination of macelignan and CTH had more beneficial effects or not. The macelignan and CTH compound significantly decreased fasting blood glucose and HbA1c compared to macelignan-treated mice, and also significantly improved postprandial glucose, insulin sensitivity, and plasma lipid profiles (FFA, and TG). On the other hand, insulin levels were not significantly changed compared to the diabetic control group. There were no significant changes in the concentrations of total cholesterol and HDL-cholesterol, but there were changes in HTR and AI. These results suggest that the macelignan and CTH compound ameliorates hyperglycemia and efficiently improves postprandial glucose, insulin sensitivity, and hyperlipidemia compared with macelignan in db/db mice. Moreover, the macelignan and CTH compound seems to be more potent in affecting diabetic complications than macelignan.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.419-426
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• 2021

In this study, we aimed to investigate the effects of 8 weeks of treatment with a combination of evogliptin and leucine, a branched-chain amino acid, in mice with high-fat diet (HFD)-induced diabetes. Treatment with evogliptin alone or in combination with leucine reduced the body weight of the mice, compared to the case for those from the HFD control group. Long-term treatment with evogliptin alone or in combination with leucine resulted in a significant reduction in glucose intolerance; however, leucine alone did not affect postprandial glucose control, compared to the case for the mice from the HFD control group. Furthermore, the combination of evogliptin and leucine prevented HFD-induced insulin resistance, which was associated with improved homeostasis model assessment for insulin resistance, accompanied by markedly reduced liver fat deposition, hepatic triglyceride content, and plasma alanine aminotransferase levels. The combination of evogliptin and leucine increased the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha, whereas those of the sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1 were not altered, compared to the case in the HFD-fed mice (p<0.05). Thus, our results suggest that the combination of evogliptin and leucine may be beneficial for treating patients with type 2 diabetes and hepatic steatosis; however, further studies are needed to delineate the molecular mechanisms underlying the action of this combination.

• Nutrition Research and Practice
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• v.18 no.1
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• pp.46-61
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• 2024

BACKGROUND/OBJECTIVES: An increasing life expectancy in society has burdened healthcare systems substantially because of the rising prevalence of age-related metabolic diseases. This study compared the effects of animal protein hydrolysate (APH) and casein on metabolic diseases using aged mice. MATERIALS/METHODS: Eight-week-old and 50-week-old C57BL/6J mice were used as the non-aged (YC group) and aged controls (NC group), respectively. The aged mice were divided randomly into 3 groups (NC, low-APH [LP], and high-APH [HP] and fed each experimental diet for 12 weeks. In the LP and HP groups, casein in the AIN-93G diet was substituted with 16 kcal% and 24 kcal% APH, respectively. The mice were sacrificed when they were 63-week-old, and plasma and hepatic lipid, white adipose tissue weight, hepatic glucose, lipid, and antioxidant enzyme activities, immunohistochemistry staining, and mRNA expression related to the glucose metabolism on liver and muscle were analyzed. RESULTS: Supplementation of APH in aging mice resulted in a significant decrease in visceral fat (epididymal, perirenal, retroperitoneal, and mesenteric fat) compared to the negative control (NC) group. The intraperitoneal glucose tolerance test and area under the curve analysis revealed insulin resistance in the NC group, which was alleviated by APH supplementation. APH supplementation reduced hepatic gluconeogenesis and increased glucose utilization in the liver and muscle. Furthermore, APH supplementation improved hepatic steatosis by reducing the hepatic fatty acid and phosphatidate phosphatase activity while increasing the hepatic carnitine palmitoyltransferase activity. Furthermore, in the APH supplementation groups, the red blood cell (RBC) thiobarbituric acid reactive substances and hepatic H₂O₂ levels decreased, and the RBC glutathione, hepatic catalase, and glutathione peroxidase activities increased. CONCLUSIONS: APH supplementation reduced visceral fat accumulation and alleviated obesity-related metabolic diseases, including insulin resistance and hepatic steatosis, in aged mice. Therefore, high-quality animal protein APH that reduces the molecular weight and enhances the protein digestibility-corrected amino acid score has potential as a dietary supplement for healthy aging.

• Journal of Life Science
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• v.31 no.1
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• pp.1-9
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• 2021

Brown seaweeds have been shown to decrease blood glucose levels and improve insulin sensitivity previously. In this study, we investigated the effect of fucoidan, a complex polysaccharide derived from brown seaweeds, on glucose uptake to improve insulin resistance, and examined its mechanism of action in 3T3-L1 adipocytes. We observed that fucoidan significantly increased glucose uptake and it was related to an increased expression of plasma membrane-glucose transporter 4 (PM-GLUT4) in 3T3-L1 adipocytes. Fucoidan treatment increased the activation of phosphatidylinositol-3-kinase (PI3K) and the phosphorylation of insulin receptor substrate 1 (IRS1tyr) compared with that of the control cells. Fucoidan also promoted the phosphorylation of Akt and protein kinase C (PKC)-λ/ζ compared to that of the control cells. Moreover, fucoidan significantly upregulated acetyl-CoA-carboxylase (ACC) and adenosine monophosphate - activated protein kinase (AMPK) phosphorylation. As a result, translocation of GLUT4 was significantly enhanced in 3T3-L1 adipocytes, which significantly promoted glucose uptake via the PI3K/AMPK pathways. The elevation of glucose uptake by fucoidan was blocked by inhibitor of PI3K and inhibitor of AMPK in 3T3-L1 adipocytes. These findings indicate that fucoidan might ameliorate glucose uptake through GLUT4 translocation to the plasma membrane by activating the PI3K/Akt and AMPK pathways in 3T3-L1 adipocytes. Fucoidan is thought to be of high material value to diabetes treatments and functional foods.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.1
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• pp.47-51
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• 2010

The objective of this study was to understand changes of plasma metabolites, hormones, and mRNA level of cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C) in liver in spontaneous clinical ketosis; 10 clinically ketotic cows and 10 healthy cows were chosen from the same dairy farm. Eleven blood parameters and liver fat content were measured in all cows, and mRNA levels of PEPCK-C in liver were measured by semi-quantitative reverse transcription (RT) polymerase chain reaction (PCR). In ketotic cows, concentration of plasma glucose decreased (p<0.01), concentration of plasma nonesterified fatty acids (NEFA) and $\beta$-hydroxybutyric acid (BHBA) increased (p<0.01), liver fat content (18.8% wet weight) and activity of plasma aspartate aminotransferase (AST) increased (p<0.01), but concentration of plasma total bilirubin (TBIL), $\gamma$-glutamyl transpeptidase ($\gamma$-GT), and cholinesterase (CHE) increased (p>0.05). In addition, concentration of plasma insulin decreased (p<0.05), concentration of plasma glucagons decreased (p>0.05), and mRNA level of PEPCK-C in liver increased (p<0.05). It is concluded that the adaptative changes of metabolites, hormones, and mRNA level of PEPCK-C in ketotic cows were in favor of the enhancement of gluconeogenesis, the decrease of fat mobilization and the relief of ketosis, but these were still inadequate to relieve ketosis.

• Preventive Nutrition and Food Science
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• v.18 no.3
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• pp.175-180
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• 2013

The purpose of this study was to determine the effects of a pre-exercise meal on the plasma human growth hormone (hGH) response and fat oxidation during walking. Subjects (n=8) were randomly provided with either 1 g/kg body weight of glucose in 200 mL water (CHO) or 200 mL water alone (CON) 30 min prior to exercise and subsequently walked on a treadmill at 50% of VO2max for 60 min. Plasma hGH concentrations were significantly higher in subjects who received CHO compared to those who received CON at 15 and 30 min. The fat oxidation rate in the CHO was significantly lower than the CON while walking for 5~15, 25~35 and 45~55 min. Plasma FFA levels were also significantly lower in the CHO compared to the CON at 30, 45 and 60 min. Plasma glucose levels in the CHO were significantly lower while plasma insulin levels were significantly higher than in the CON at 15 and 30 min. Therefore, the results of this study suggest that the elevation of plasma hGH levels due to the intake of a pre-exercise meal may not be strongly related to fat oxidation and plasma free fatty acid (FFA) levels during low-intensity exercise.

• Journal of Nutrition and Health
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• v.37 no.4
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• pp.259-265
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• 2004

This study was designed to examine the effects of diets containing different levels of seeds of Benincasa hispida (wax-gourd)on plasma glucose, insulin levels and lipid profiles in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were induced diabetes mellitus by STZ injection (45 mg/kg) into the tail vein and were divide into 4 groups: normal, STZ-control, two experimental groups. Normal and STZ-control groups were fed an AIN-93 diet and 2 experi-mental groups were fed a modified diet containing 2.5% and 5.0% of wax gourd seed powder for 4 weeks. The weight gain and feed efficiency ratio in 5.0% seed groups were higher than in STZ-control group. A significant lowering effects of plasma glucose levels were observed in the wax gourd seed 2.5% and 5.0 groups. The plasma insulin level did not differ after treatment with wax gourd seed in experimental rats. The intake of 2.5% wax gourd seed did not result in sig-nificant change in plasma cholesterol levels compared to diabetic control group. The intake of 2.5% wax gourd seeds had normalized the increased levels of plasma triglyceride and free fatty acids after 4 weeks. In 5% wax gourd seed group, cholesterol, triglyceride and free fatty acid levels were elevated compared to 2.5% wax gourd seed group. The results of the present study indicate that 2.5% wax gourd seed group would be more effective to control the diabetes than 5% wax gourd seed group.

• Journal of Oriental Neuropsychiatry
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• v.21 no.4
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• pp.53-68
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• 2010

Objectives : We investigated the effects of Sopungsungj-won(Shufengshunqjvuan) (SSEx1, SSEx2) on the metabolic syndrome in high-fat diet induced obese mice. Methods: 8 weeks old, high fat diet induced obese male mice were divided into 4 groups: C57BL/6 lean control, obese vehicle control, SSEx1, SSEx2. After mice were treated with SSExl, SSEx2 for 12 weeks, we measured body weight gain, food intake, feeding efficiency ratio, fat weight, plasma leptin, insulin, glucose and lipid levels. We also observe the morphology and count for the numbers of Adipocyte and evaluate the weight of organs and it's function. Results: 1. Compared to Obese Control Group, SSEx1 gained significantly lower body weight and showed lower Feeding Efficiency Ratio. 2. Compared to Obese Control Group, SSEx1 showed lower weights of epididymal adipose tissue, troperitoneal adipose tissue, inguinal adipose tissue, brown adipose tissue. SSEx2 showed higher weights of epididymal adipose tissue, troperitoneal adipose tissue, inguinal adipose tissue, brown adipose tissue. 3. Compared to Obese Control Group, the size of adipocytes was significantly decreased by SSEx1, whereas the number of adipocites per unit was significantly increased. Hepatic lipid accumulation was decreased significantly by SSEx1. 4. Concerning the weights of Liver, Heart, Spleen, Kidney and Pancreas, SSEx1, SSEx2 showed little differences with those of Lean Control, Obese Control. 5. Compared to Obese Control Group, SSEX1, SSEx2 showed lower level of plasma triglyceride, but SSEx1 had significance only. SSEx1, SSEx2 showed little lower level of plasma HDL-cholesterol. LDL-cholesterol, total cholesterol, but had no significances. 6. Concerning the levels of plasma glucose, insulin and leptin, SSEx1 and SSEx2 showed littele changes with those of Lean Control, Obese Control. 7. The leves of Plasma AST, AST, ALT, free fatty acid, BUN, creatinine were in the physiological range at 4 groups all: Lean Control, Obese Control, SSEx1, SSEx2. Conclusions : These results showed SSEx1 can be used as therapeutic agent for Obesity and metabolic syndrome caused by long-period high fat diet.

• Journal of the Korean Society of Food Culture
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• v.22 no.1
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• pp.157-165
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• 2007

This study was designed to evaluate the effects of fructose(F) or sucrose(S) and guar gum intake on carbohydrate and lipid metabolism in 15-week-old male Goto-Kakizaki(GK) rats. Fifty rats were randomly assigned to 5 groups which were different in carbohydrate(25% of carbohydrate) and fiber(5% w/w) sources. The carbohydrate(CHO) sources of each group were comstarch(control group, 100% of CHO), fructose with cellulose(F), fructose with guar gum(FG), sucrose with cellulose(S), and sucrose with guar gum(SG). Each group was fed exterimental diet for 4 weeks. We measured food intake, body weight gain, adipose tissues weight and organs weight. We conducted oral glucose tolerance test(OGTT) and measured plasma insulin concentration to examine carbohydrate metabolism. To evaluate lipid metabolism, we measured the lipid profile of plasma, liver and feces. Food intake and weight gain of FG or SG groups tended to be less than those of F or S groups. Perirenal and epididymal fat pad weights of SG group were significantly lower than those of S group and those of FG group tended to be lower than those of F group. In OGTT, blood glucose values of F or S groups were significantly higher than those of C group, and FG or SG groups tended to be lower than those of F or S groups during the experimental time. The area under the curve(AUC) of C group was significantly highest among the groups, AUC and plasma insulin concentration of FG or SG groups tended to be lower than those of F or S groups. Plasma and hepatic triglyceride (TG) of FG and SG groups were significantly lower than those of F and S groups, plasma and hepatic total lipid(TL) and total cholesterol(TC) of FG and SG groups tended to be lower than those of F and S groups. Fecal TL, TG and TC of FG or SG groups tended to be higher than those of F and S groups. In conclusion, intake of guar gum should improve carbohydrate and lipid metabolism in partial substitution of fructose or sucrose for cornstarch in GK rats.