• Nutrition Research and Practice
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• 제5권3호
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• pp.205-213
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• 2011

Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC- $1{\alpha}$, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes. Forty GK rats either remained sedentary (SED), performed ET, received SEL, ($5\;{\mu}mol{\cdot}kg$ body $wt^{-1}{\cdot}day^{-1}$) or underwent both ET and SEL treatment for 6 wk. ET alone, SEL alone, or COMBI resulted in a significant lowering of lactate, glucose, and insulin levels as well as a reduction in HOMA-IR and AUC for glucose relative to SED. Additionally, ET alone, SEL alone, or COMBI increased glycogen content and citrate synthase (CS) activities in liver and muscles. However, their effects on glycogen content and CS activity were tissue-specific. In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-la, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED. However, their effects on glucose and lactate metabolic proteins also appeared to be tissue-specific. It seemed that glucose and lactate metabolic protein expression was not further enhanced with COMBI compared to that of ET alone or SEL alone. These data suggest that ET alone or SEL alone or COMBI represent a practical strategy for ameliorating aberrant expression of glucose and lactate metabolic proteins in diabetic GK rats.

• Nutrition Research and Practice
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• 제11권3호
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• pp.180-189
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• 2017

BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS: Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha ($HNF-1{\alpha}$), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta ($GSK-3{\beta}$) expression levels. The ${\alpha}-glucosidase$ inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS: CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through $HNF-1{\alpha}$ expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and $GSK-3{\beta}$, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of ${\alpha}-glucosidase$ inhibitory activity than that from acarbose. CONCLUSION: CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.

• Nutrition Research and Practice
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• 제11권3호
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• pp.198-205
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• 2017

BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.581-593
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• 2016

The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.

• 한국식품영양학회지
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• 제22권3호
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• pp.456-462
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• 2009

Adlay, barley and rice bran were extracted using various concentrations of methanol(10% and 80%) and chloroform : methanol(2 : 1) to examine the biological activities of these raw grains. Extraction with 80% methanol resulted in high Vitamin C Equivalent Antioxidant Capacity(VCEAC), in the order of barley > rice bran > adlay, as determined by DPPH and ABTS assays. In addition, the extracts of adlay and rice bran showed high cellular antioxidant activity in HepG2 cells possibly due to the presence of polyphenol glycosides in these grains. We examined the expression of glucose/fatty acid metabolizing genes in differentiated 3T3-L1 adipocyte cells. Glut1 was downregulated after treatment with rice bran and no changes in the expression of Glut4 was observed. In contrast, genes involved in fatty acid metabolism, CD36 and aP2, were upregulated. Since these physiological changes were matched with peroxisome proliferator activating receptor $\gamma$(PPAR $\gamma$) agonism, we suggest that the extracts from adlay, barley and rice bran may play preventive roles against aging and diabetes via antioxidant activity and increased uptake of fatty acids by adipocytes.

• 한국식품과학회지
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• 제52권1호
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• pp.81-88
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• 2020

PGSE의 혈당조절 효과를 평가하기 위하여 제2형 당뇨 동물모델을 이용하여 8주간의 동물실험을 진행한 결과, 고농도 PGSE(600 mg/kg)의 투여는 경구 포도당 내성 및 혈당 수준을 유의적으로 감소시켰으며(p<0.05), 당화혈색소도 유의적으로 낮은 수준을 유지시켰다(p<0.05). 또한, 혈청 인슐린과 렙틴 농도 역시 대조군과 비교하여 PGSE 고농도 처리군에서 유의적으로 감소하였다(p<0.05). PGSE 투여는 db/db 마우스의 골격근에서 인슐린 의존적 세포신호전달경로를 유의적으로 활성화시켰으며, AMPK 인산화를 촉진시키고, 골격근내 포도당 흡수를 위한 GLUT4의 세포막으로의 전이를 대조군 대비 약 1.7배 증가시켰다. 이러한 결과를 근거로 할 때 PGSE는 항 당뇨병 치료제로서의 잠재적 가능성을 가진 것으로 판단된다.

• Fisheries and Aquatic Sciences
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• 제23권9호
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• pp.24.1-24.9
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• 2020

Brown alga (Ishige okamurae; IO) dietary supplements have been reported to possess anti-diabetic properties. However, the effects of IO supplements have not been evaluated on glucose metabolism in the pancreas and skeletal muscle. C57BL/6 N male mice (age, 7 weeks) were arranged in five groups: a chow diet with 0.9% saline (NFD/saline group), high-fat diet (HFD) with 0.9% saline (HFD/saline group). high-fat diet with 25 mg/kg IO extract (HFD/25/IOE). high-fat diet with 50 mg/kg IO extract (HFD/50/IOE), and high-fat diet with 75 mg/kg IO extract (HFD/75/IOE). After 4 weeks, the plasma, pancreas, and skeletal muscle samples were collected for biochemical analyses. IOE significantly ameliorated glucose tolerance impairment and fasting and 2 h blood glucose level in HFD mice. IOE also stimulated the protein expressions of the glucose transporters (GLUTs) including GLUT2 and GLUT4 and those of their related transcription factors in the pancreases and skeletal muscles of HFD mice, enhanced glucose metabolism, and regulated blood glucose level. Our results suggest Ishige okamurae extract may reduce blood glucose levels by improving glucose metabolism in the pancreas and skeletal muscle in HFD-induced diabetes.

• 생약학회지
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• 제43권4호
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• pp.308-315
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• 2012

Opuntia humifusa known as the Eastern prickly pear have been used as a treatment of burns, diarrhea, asthma, rheumatism, gonorrhea, and diabetes in alternative medicine. O. humifusa is widely cultivated in the middle and southern provinces of Korea and distributed in North America. The aim of this study is to investigate anti-diabetic effect of O. humifusa stem (OHS) water or 80% MeOH extract using 3T3-L1 adipocytes and db/db mice animal models. OHS 80% MeOH extract at a dose of $250{\mu}g/ml$ significantly increased the glucose uptake and lipid accumulation compared with the control in 3T3-L1 adipocytes. Blood glucose, plasma total cholesterol and triglyceride levels were significantly reduced by oral treatment of OHS 80% MeOH extract (200 mg/kg BW) for 6 weeks in db/db mice. Also, the oral treatment of OHS 80% MeOH extract slightly changed the plasma insulin and insulin resistance levels in db/db mice, but were no significance in comparison to control. Glucose transporter(GLUT)4 expressions of adipose tissue and muscle were significantly increased more than that in the control. Therefore, these results suggest that OHS 80% MeOH extract inhibits the blood glucose level through regulation of lipid profile, insulin resistance, and GLUT4 expression in db/db mice and its diabetic effect is effective more than water extract.

• Molecules and Cells
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• 제38권5호
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• pp.452-456
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• 2015

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals ($BMI{\geq}30kg/m^2$) showed significantly increased hypermethylation for IL6 gene compared to normal weight ($BMI<23kg/m^2$) and overweight sample ($23kg/m^2{\leq}BMI<30kg/m^2$) (P = 0.034 and P = 0.026). However there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.220-225
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• 2012

To develop a ginseng product possessing an efficacy for diabetes, ginseng radix ethanol extract was treated with pectinase and obtained the GINST. In the present study, we evaluate the beneficial effect of GINST on high fat diet (HFD)-induced hyperglycemia and hyperlipidemia and action mechanism(s) in ICR mice. The mice were randomly divided into five groups: regular diet group (RD), high fat diet group (HFD), HFD plus GINST at 75 mg/kg (GINST75), 150 mg/kg (GINST150), and 300 mg/kg (GINST300). Oral glucose tolerance test reveals that GINST improves the glucose tolerance after glucose challenge. Fasting plasma glucose and insulin levels were decreased by 4.3% and 4.2% in GINST75, 10.9% and 20.0% in GINST150, and 19.6% and 20.9% in GINST300 compared to those in HFD control group. Insulin resistance indices were also markedly decreased by 8.2% in GINST75, 28.7% in GINST150, and 36.4% in GINST300, compared to the HFD control group. Plasma triglyceride, total cholesterol and non-esterified fatty acid levels in the GINST300 group were decreased by 13.5%, 22.7% and 24.1%, respectively, compared to those in HFD control group. Enlarged adipocytes of HFD control group were markedly decreased in GINST-treated groups, and shrunken islets of HFD control mice were brought back to near normal shape in GINST300 group. Furthermore, GINST enhanced phosphorylation of AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). In summary, GINST prevents HFD-induced hyperglycemia and hyperlipidemia through reducing insulin resistance via activating AMPK-GLUT4 pathways, and could be a potential therapeutic agent for type 2 diabetes.