• Nutrition Research and Practice
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• v.7 no.6
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• pp.446-452
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• 2013

Chronic consumption of a high-fat, high-sucrose (HFHS) diet increases insulin resistance and results in type 2 diabetes mellitus in C57BL/6J mice. Hyperglycemia in diabetics increases oxidative stress, which is associated with a high risk of diabetic complications. The purpose of this study was to examine the hypoglycemic and antioxidant effects of chamnamul [Pimpinella brachycarpa (Kom.) Nakai] in an animal model of type 2 diabetes. The ${\alpha}$-glucosidase inhibitory activity of a 70% ethanol extract of chamnamul was measured in vitro. Five-week-old male C57BL/6J mice were fed a basal or HFHS diet with or without a 70% ethanol extract of chamnamul at a 0.5% level of the diet for 12 weeks after 1 week of adaptation. After sacrifice, serum glucose, insulin, adiponectin, and lipid profiles, and lipid peroxidation of the liver were determined. Homeostasis model assessment for insulin resistance (HOMA-IR) was determined. Chamnamul extract inhibited ${\alpha}$-glucosidase by 26.7%, which was 78.3% the strength of inhibition by acarbose at a concentration of 0.5 mg/mL. Serum glucose, insulin, and cholesterol levels, as well as HOMA-IR values, were significantly lower in the chamnamul group than in the HFHS group. Chamnamul extract significantly decreased the level of thiobarbituric acid reactive substances and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in the liver compared with the HFHS group. These findings suggest that chamnamul may be useful in prevention of hyperglycemia and reduction of oxidative stress in mice fed a HFHS diet.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.185-194
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• 2018

The different polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene promote variances in diabetes susceptibility in humans. We investigated whether these genotypes also promote differences in diabetic susceptibility in commercial pigs. Growing pigs (Landrace, both sex, 50-60 kg) with the C/C (n=4) and T/T (n=5) TCF7L2 genotypes were identified and intravenously injected with streptozotocin (STZ, 40 mg/kg) twice in weekly intervals, then a high-energy diet was offered. Oral glucose tolerance tests, blood analyses and the homeostasis model assessment-insulin resistance (HOMA-IR) index calculations were performed. The animals were sacrificed at the end of 12 weeks of treatment to reveal the pancreas histomorphometry. The results showed that all of the treated pigs grew normally despite exhibiting hyperglycemia at two weeks after the induction. The glycemic level of the fasting or postprandial pigs gradually returned to normal. The fasting insulin concentration was significantly decreased for the T/T carriers but not for the C/C carriers, and the resulting HOMA-IR index was significantly increased for the C/C genotype, indicating that the models of insulin dependence and resistance were respectively developed by T/T and C/C carriers. The histopathological results illustrated a significant reduction in the pancreas mass and insulin active sites, which suggested increased damage. The results obtained here could not be compared with previous studies because the TCF7L2 background has not been reported. Growing pigs may be an excellent model for diabetic in children if the animals are genetically pre-selected.

• Journal of agricultural medicine and community health
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• v.43 no.1
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• pp.18-30
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• 2018

Objectives: This study was conducted to examine the association of serum Vitamin D with insulin resistance and ${\beta}-cell$ function in Korean health checkup examinees. Methods: This study subjects were 374 healthy adults (199 males, 175 females) over the age of 20, who visited a general hospital medical center located in Haenam-gun, Jeollanam-do. To find the association of Vitamin D with HOMA-IR and $HOMA-{\beta}$, the used statistical analysis were ANOVA and ANCOVA. Results: Of the study subjects, the level of serum Vitamin D defined by deficient group, insufficient group and sufficient group was 38.5%, 48.1% and 13.4%, respectively. According to the level of serum Vitamin D, the mean values of HOMA-IR were $1.92{\pm}1.08$ in sufficient group, $1.99{\pm}1.04$ in the insufficient group and $2.91{\pm}1.05$ in deficient group and there were statistically significant different(p<0.001). The mean values of $HOMA-{\beta}$ were $84.69{\pm}1.07$ in sufficient group, $78.41{\pm}1.04$ in the insufficient group and $80.48{\pm}1.04$ in deficient group, and there were not significant. As a result of ANCOVA, adjusted mean of HOMA-IR were statistically significant different (p<0.001), but those of $HOMA-{\beta}$ were not statistically significant according to the level of serum Vitamin D. Conclusion: The insufficient level of serum Vitamin D was relatively high in healthy adults who live in rural area, and it was found that HOMA-IR significantly increased when Vitamin D was deficient. To prevent insulin resistance or diabetes, it is necessary to provide sufficient information related to sufficient production of Vitamin D such as Vitamin D supplement, sun exposure, food intake and etc.

• Clinical and Experimental Pediatrics
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• v.50 no.10
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• pp.987-994
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• 2007

Purpose : This study investigated the clinical significance of AN in children and adolescents with obesity induced metabolic complications. Methods : Forty-nine patients who had obesity induced metabolic complications were participated in this cross-sectional study. Obesity induced metabolic complications are as follows: hypertension, dyslipidemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), nonalcoholic steatohepatitis (NASH), homeostasis model assessment of insulin resistance (HOMA-IR)>3.16. Clinical characteristics, such as, age, percentage-weight-for-height (PWH), pubertal status, blood pressure (BP), fasting plasma insulin level, fasting and post-oral glucose tolerance test 2-hour glucose levels, liver function test, lipid profile, HOMA-IR were compared according to the presence of AN. Results : Sixty-five percent of patients had AN, 57.1% NASH, 57.1% dyslipidemia, 55.1% hypertension, 46.9% IFG, 24.5% HOMA-IR>3.16 and 16.2% IGT. The patients who were moderately to severely obese with AN had higher incidence of IGT and HOMA-IR>3.16. The patients with AN had significantly higher diastolic BP ($79.4{\pm}6.9$ vs $75.4{\pm}5.6mmHg$), fasting levels of plasma insulin ($10.6{\pm}6.0$ vs $6.2{\pm}5.4{\mu}IU/mL$), HOMA-IR index ($2.6{\pm}1.4$ vs $1.4{\pm}1.3$) and PWH ($42.4{\pm}13.0$ vs $34.3{\pm}1.8%$). The increasing tendency for the presence of AN was significantly related to the cumulative number of obesity induced metabolic complications. Binary logistic regression analysis revealed that the presence of AN was significantly associated with fasting plasma insulin level, PWH and IFG. Conclusion : AN could be useful as a clinical surrogate of obesity induced metabolic complications.

• Journal of Preventive Medicine and Public Health
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• v.43 no.1
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• pp.1-8
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• 2010

Objectives: This study was performed to investigate if organochlorine pesticides (OCPs) were associated with metabolic syndrome and insulin resistance among non-diabetes. Methods: Among subjects who participated in a community-based health survey, 50 non-diabetic subjects with metabolic syndrome and 50 normal controls were selected. Insulin resistance was measured by the homeostasis model assessment (HOMA-IR). Eight OCPs were selected. Results: After adjusting for confounders except for body mass index (BMI), beta-hexachlorocyclohexane ($\beta$-HCH) and heptachlor epoxide were positively associated with metabolic syndrome. Odds ratios across tertiles of $\beta$-HCH and heptachlor epoxide were 1.0, 3.2 and 4.4, and 1.0, 4.0 and 6.0, respectively (p for trend = 0.01 and <0.01). After additional adjustment for body mass index (BMI), heptachlor epoxide still showed an increasing trend with adjusted odds ratios of 1.0, 4.1, and 4.6 (p for trend = 0.10). When the five components of metabolic syndrome (with the definition of high fasting glucose ($\geq$ 100 mg/dL) were separately analyzed, all components were positively, but not significantly, associated with heptachlor epoxide. As the serum concentration of heptachlor epoxide increased, HOMA-IR increased significantly in subjects with metabolic syndrome even after adjusting for BMI (p value <0.05 and <0.01). Conclusions: Despite the small sample size, this study suggests that the background exposure to some OCPs may be associated with metabolic syndrome.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.544-549
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• 2014

BACKGROUND/OBJECTIVES: Obesity-associated insulin resistance is a strong risk factor for type 2 diabetes mellitus. The aim of this study was to investigate the effect of myricetin on adiposity, insulin resistance, and inflammatory markers in mice with diet-induced insulin resistance. MATERIALS/METHODS: Five-week-old male C57BL/6J mice were fed a basal diet, a high-fat, high-sucrose (HFHS) diet, or the HFHS diet containing 0.06% myricetin or 0.12% myricetin for 12 weeks after a 1-week adaptation, and body weight and food intake were monitored. After sacrifice, serum lipid profiles, glucose, insulin, adipocyte-derived hormones, and proinflammatory cytokines were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. RESULTS: Myricetin given at 0.12% of the total diet significantly reduced body weight, weight gain, and epidydimal white adipose tissue weight, and improved hypertriglyceridemia and hypercholesterolemia without a significant influence on food intake in mice fed the HFHS diet. Serum glucose and insulin levels, as well as HOMA-IR values, decreased significantly by 0.12% myricetin supplementation in mice fed the HFHS diet. Myricetin given at 0.12% of the total diet significantly reduced serum levels of leptin, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) in mice fed the HFHS diet. CONCLUSIONS: These findings suggest that myricetin may have a protective effect against diet-induced obesity and insulin resistance in mice fed HFHS diet, and that alleviation of insulin resistance could partly occur by improving obesity and reducing serum proinflammatory cytokine levels.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.206-213
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• 2017

BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin $F2{\alpha}$ (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

• Nutrition Research and Practice
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• v.11 no.3
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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.

• Korean journal of food and cookery science
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• v.30 no.4
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• pp.369-377
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• 2014

Obesity increases oxidative stress, which could contribute to the development of insulin resistance and hyperglycemia. The purpose of this study was to investigate the hypoglycemic and antioxidant effect of sanchae-namul (SN) in mice with diet-induced obesity. Five-week-old male C57BL/6J mice were fed a basal or high-fat and high-sucrose (HFHS) diet with or without 3% freeze-dried SN powder composed of chamnamul, daraesoon, miyeokchwi, bangpung namul, and samnamul for 12 weeks after a 1-week adaptation. After sacrifice, serum glucose and insulin were measured and the homeostasis model assessment for insulin resistance (HOMA-IR) was determined as well. Hepatic lipid peroxidation, glutathione (GSH), and activities of the antioxidant enzymes were determined. SN given at 3% of the total diet did not significantly influence body weight and food intake in mice fed the HFHS diet. Serum glucose and insulin levels, as well as HOMA-IR values, were significantly lower in the SN group than those in the HFHS group. Thiobarbituric acid reactive substances (TBARS) levels in the liver were decreased significantly in the SN group compared with those in the HFHS group. SN significantly increased the GSH levels and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver compared with those in the HFHS group. Overall, these findings suggest that SN may be useful in alleviating insulin resistance and hyperglycemia in mice fed HFHS diet; further, the improvement of insulin resistance could partly occur by reducing the oxidative stress.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.328-335
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• 2016

BACKGROUND/OBJECTIVES: Vitamin D plays an important role in the etiology of gestational diabetes mellitus (GDM). This study evaluated the effect of vitamin D supplementation on metabolic indices and hs-C-reactive protein (CRP) levels in GDM patients. SUBJECTS/METHODS: The study was a randomized, placebo-controlled, double-blinded clinical trial. Seventy-six pregnant women with GDM and gestational age between 24-28 weeks were assigned to receive four oral treatments consisting of 50,000 IU of vitamin $D_3$ (n = 38) or placebo (n = 38) once every 2 weeks for 2 months. Fasting blood glucose (FG), insulin, HbA1c, 25-hydroxyvitamin D, lipid profile, hs-CRP, and homeostasis model assessment-insulin resistance (HOMA-IR) were measured before and after treatment. Independent and paired t-tests were used to determine intra- and intergroup differences, respectively. ANCOVA was used to assess the effects of vitamin D supplementation on biochemical parameters. RESULTS: Compared with the placebo group, in the vitamin D group, the serum level of 25-hydroxyvitamin D increased (19.15 vs. -0.40 ng/ml; P < 0.01) and that of FG (-4.72 vs. 5.27 mg/dl; P = 0.01) as well as HbA1c (-0.18% vs. 0.17%; P = 0.02) decreased. Improvements in the lipid profiles were observed in the vitamin D group, but without statistical significance. Significant increases in concentrations of hs-CRP, FG, HbA1c, total cholesterol, and LDL cholesterol were observed in the placebo group. No significant change in fasting insulin and HOMA-IR was observed in either group. CONCLUSIONS: In GDM patients, vitamin D supplementation improved FG and HbA1c but had no significant effects on lipid profile or hs-CRP.