• Journal of Nutrition and Health
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• 제39권4호
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• pp.323-330
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• 2006

Peripheral insulin resistance in obese/type II diabetes animals results from an impairment of insulin-stimulated glucose uptake into skeletal muscle. Insulin stimulate the translocation of GLUT4 from intracellular location to the plasma membrane. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) is implicated in mediation of fusion of GLUT4-containing vesicle with the plasma membrane. Present study investigated regulatory effects of Rhodiola sachalinensis administration and exercise training on the expression of GLUT4 protein and SNAREs protein in skeletal muscles of obese Zucker rats. Experimental animals were randomly assigned into one of five groups ; lean control(LN), obese control(OB), exercise-treated(EXE), Rhodiola sachalinensis-treated(Rho), combine of Rho & EXE (Rho-EXE). All animals of exercise training (EXE, Rho-EXE) performed treadmill running for 8 weeks, and animals of Rho groups (Rho, Rho-EXE) were dosed daily by gastric gavage during the same period. After experiment, blood were taken for analyses of glucose, insulin, and lipids levels. Mitochondrial oxidative enzyme (citrate synthase, CS ; $\beta$-hydroxyacyl-CoA dehydrogenase, $\beta$-HAD) activity were analysed. Skeletal muscles were dissected out for analyses of proteins (GLUT4, VAMP2, syntaxin4, SNAP23). Results are as follows. Exercise and/or Rhodiola sachalinensis administration significantly reduced body weight and improved blood lipids (TG, FFA), and increased insulin sensitivity. Endurance exercise significantly increased the activity of mitochondrial enzymes and the expression of GLUT4 protein, however, administration of Rhodiola sachalinensis did not affect them. The effect of exercise and/or Rhodiola sachalinensis administration on the expression of SNARE proteins was unclear. Our study suggested that improvement insulin sensitivity by exercise and/or Rhodiola sachalinensis administration in obese Zucker rats is independent of expression of SNARE proteins.

• 대한물리의학회지
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• 제13권1호
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• pp.11-26
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• 2018

PURPOSE: The aim of this study was to review the effects of exercise intervention on blood glucose control in obese type 2 diabetic patients. METHODS: The PubMed and KERISS search engines were used and 61 papers that met the key questions were selected. RESULTS: Exercise is an effective intervention for the control of blood glucose in type 2 diabetic patients because it does not impair glucose transport in the skeletal muscle induced by muscle contractions. Insulin resistance, which is characteristic of type 2 diabetes, is caused by decreased insulin sensitivity or insulin responsiveness. Acute exercise improves the glucose metabolism by increasing the insulin-independent signaling pathways and insulin sensitivity in the skeletal muscle, and regular long-term exercise improves the skeletal muscle insulin responsiveness and systemic glucose metabolism by increasing the mitochondrial and GLUT4 protein expression in the skeletal muscle. CONCLUSION: The improvement of the glucose metabolism through exercise shows a dose-response pattern, and if exercise consumes the same number of calories, high intensity exercise will be more effective for the glucose metabolism. On the other hand, it is practically difficult for a patient with obese type 2 diabetes to control their blood glucose with high intensity or long-term exercise. Therefore, it will be necessary to study safe adjuvants (cinnamic acid, lithium) that can produce similar effects to high-intensity and high-volume exercises in low-intensity and low-volume exercises.

• Journal of Nutrition and Health
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• 제56권4호
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• pp.349-360
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• 2023

Purpose: Ketogenic diets (KDs) have anti-obesity effects that may be related to glucose control and the gut microbiota. This paper hypothesizes that KD reduces body weight and changes the insulin sensitivity and gut microbiota composition in a mouse model of diet-induced obesity. Methods: In this study, C57BL/6 male mice were assigned randomly to 3 groups. The assigned diets were provided to the control and high-fat (HF) diet groups for 14 weeks. The KD group was given a HF diet for 8 weeks to induce obesity, followed by feeding the KD for the next 6 weeks. Results: After the treatment period, the KD group exhibited a 35.82% decrease in body weight gain compared to the HF group. In addition, the KD group demonstrated enhanced glucose control, as shown by the lower levels of serum fasting glucose, serum fasting insulin, and the homeostatic model assessment of insulin resistance, compared to the HF group. An analysis of the gut microbiota using 16S ribosomal RNA sequencing revealed a significant decrease in the proportion of Firmicutes when the KD was administered. In addition, feeding the KD reduced the overall alpha-diversity measures and caused a notable separation of microbial composition compared to the HF diet group. The KD also led to a decrease in the relative abundance of specific species, such as Acetatifactor_muris, Ligilactobacillus_apodemi, and Muribaculum_intestinale, compared with the HF group. These species were positively correlated with the body weight, whereas the abundant species in the KD group (Kineothrix_alysoides and Saccharofermentans_acetigenes) showed a negative correlation with body weight. Conclusion: The current study presents supporting evidence that KD reduced the body weight and altered the insulin sensitivity and gut microbiota composition in a mouse model of diet-induced obesity.

• 한국식품영양학회지
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• 제11권5호
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• pp.550-555
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• 1998

The purpose of this study was to investigate the effects of n-3 polyunsaturated fatty acids(PUFA) on glucose and lipids metabolism in high-fat diet rate. Rats were randomly assigned to normal, high-fat with n-3 PUFA and high-fat dietary groups. Experiments were carried out after 5 weeks feeding with prescriptive diets following 7 hrs fasting. Body weight gains tended to be higher in high-fat fed rats than normal. Blood glucose was increased (p<0.05) by high-fat diet compared with normal diet, and decreaseed (p<0.05) to normal level by n-3 PUFA. Plasma insulin level was significcantly higher (p<0.01) in high-fat diet rats than that of normal-diet rats, and also decreased (p<0.01) by n-3 PUFA. Glucose up take of soleus muscle in vitro was decreased markedly in high-fat fed rats than normal diet rats at 0, 1, 10, and 100nM insulin concentration. Therefore insulin sensitivity and responsiveness were decreased by high-fat diet. Omega-3 PUFA made a recover(p<0.01) insulin sensitivity to almost normal level, and improved (p<0.05) insulin responsiveness in some extent. In conclusion, the results suggest that metabolic disorder of glucose and insulin resistance of skeletal muscle are caused by high-fat diet and n-3 PUFA can ameliorate metabolic disorder and insulin resistance.

• Clinical and Experimental Pediatrics
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• 제48권8호
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• pp.857-864
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• 2005

목 적 : 인슐린 감수성 지표들은 신체계측지수인 체질량지수 및 비만도와 상관관계를 보이는 것으로 알려져 있다. 그러나 이러한 신체계측지수들이 체지방량을 잘 반영하는 것으로 알려져 있기는 하나 소아에서는 성인에 비해 그 정확도가 떨어지므로 실제로 측정한 체지방량과 인슐린 감수성 지표들 간에도 이와 같은 연관성이 있는지에 대한 연구는 없는 실정이다. 따라서 본 연구에서는 단순 소아 비만아들을 대상으로 하여, 체지방측정에 있어 비교적 객관적이며 정확한 방법으로 알려진 BIA와 DEXA로 측정한 체지방량과 인슐린 감수성 지표들 간에 어떠한 연관성이 있는지 알아보고 추후 외래에서 비만아들을 추적 관찰할 때 어느 지표가 가장 유용한지 알아보고자 한다. 방 법 : 2002년 1월부터 2004년 7월까지 중앙대학교 용산병원 비만클리닉을 방문한 28명의 단순비만 환자를 대상으로 하였다. 12시간 이상 금식 후 채혈을 하여 혈당과 인슐린 수치를 측정하였다. 같은 날 신장, 체중, 허리 둘레, 엉덩이 둘레를 계측하였고, BIA와 DEXA를 시행하여 체지방량을 구하였다. 얻어진 혈당과 인슐린 수치를 이용하여 G/I ratio, $log_{insulin}$, HOMA-IR, $log_{HOMA-IR}$, QUICKI를 구하여 체지방량과의 연관성을 알아보았다. 결 과 : 1) 인슐린 감수성 지표 중 G/I ratio만 triglyceride와 통계상 연관성이 있는 것으로 나왔다(r=-0.206, P<0.05). 이외의 $log_{insulin}$, HOMA-IR, $log_{HOMA-IR}$, QUICKI는 혈중 지질치와 관련이 없었다. 2) 비만도는 G/I ratio와 -0.209(P<0.05), $log_{insulin}$과 0.196(P<0.05), HOMA-IR과 0.238(P<0.01), $log_{HOMA-IR}$과 0.198(P<0.05), QUICKI와는 -0.224(P<0.05)로 연관성이 있는 것으로 나왔고, 체질량지수는 G/I ratio와 -0.463(P<0.01), $log_{insulin}$과 0.417(P<0.05), HOMA-IR과 0.301(P<0.01), $log_{HOMA-IR}$과 0.403(P<0.01), QUICKI와는 -0.451(P<0.01)로 나와 비만도 보다 더 인슐린 감수성 지표들과 상관성이 높은 것으로 나타났다. 3) BIA로 측정한 체지방량과 비만도 및 체질량지수 각각에 대한 상관계수는 0.612(P<0.01), 0.316(P<0.05)으로 나왔고, DEXA로 측정한 체지방량과는 각각 0.667(P<0.01), 0.512(P<0.05)로 나와 체지방량과 비만도 및 체질량지수 사이에 연관성이 있는 것으로 밝혀졌다. 4) G/I ratio는 BIA로 측정한 체지방량 및 체지방률과 각각 상관계수 -0.420(P<0.05), -0.366(P<0.05)으로 상관성을 보이고 있었고, DEXA로 측정한 체지방량 및 체지방률과도 -0.512(P<0.01), -0.449(P<0.01)로 높은 상관성을 보였다. HOMA-IR은 DEXA로 측정한 체지방량과만 상관계수 0.341(P<0.05)로 연관성을 나타냈고, 그밖에 다른 인슐린 감수성 지표들은 체지방량 및 체지방률 모두와 상관성이 없었다. 결 론 : 인슐린 감수성 지표들과 비만도 및 체질량지수와 같은 신체 계측지수들 간의 상관성에서, 인슐린 감수성 지표 특히 G/I ratio가 비만도 및 체질량지수 모두와 높은 상관성을 보였고, 체지방량 및 체지방률과 인슐린 감수성 지표와의 관계에서는 G/I ratio만이 BIA와 DEXA로 측정한 체지방량과 체지방률 모두와 연관성이 있는 것으로 나타났다. 따라서 단순 비만아의 진단 및 추적 관찰시 BMI 및 인슐린과 혈당치를 기초로 한 인슐린 감수성 지표 특히, G/I ratio의 활용이 임상에서 유용하게 사용될 수 있을 것으로 생각된다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제19권4호
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• pp.251-258
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• 2016

Purpose: This study aimed to evaluate the utility of acanthosis nigricans (AN) severity as an index for predicting insulin resistance in obese children. Methods: The subjects comprised 74 obese pediatric patients who attended the Department of Pediatrics at Chosun University Hospital between January 2013 and March 2016. Waist circumference; body mass index; blood pressure; fasting glucose and fasting insulin levels; lipid profile; aspartate transaminase, alanine transaminase, glycated hemoglobin, C-peptide, and uric acid levels; and homeostatic model assessment insulin resistance (HOMA-IR) and quantitative insulin check sensitivity index (QUICKI) scores were compared between subjects with AN and those without AN. Receiver operating characteristic curves were used to investigate the utility of the AN score in predicting insulin resistance. HOMA-IR and QUICKI were compared according to AN severity. Results: The With AN group had higher fasting insulin levels ($24.1{\pm}21.0\;mU/L$ vs. $9.8{\pm}3.6\;mU/L$, p<0.001) and HOMA-IR score ($5.74{\pm}4.71$ vs. $2.14{\pm}0.86$, p<0.001) than the Without AN group. The AN score used to predict insulin resistance was 3 points or more (sensitivity 56.8%, specificity 83.9%). HOMA-IR scores increased with AN severity, from the Without AN group (mean, 2.15; 95% confidence interval [CI], 1.72-2.57) to the Mild AN (mean, 4.15; 95% CI, 3.04-5.25) and Severe AN groups (mean, 7.22; 95% CI, 5.08-9.35; p<0.001). Conclusion: Insulin resistance worsens with increasing AN severity, and patients with Severe AN (AN score ${\geq}3$) are at increased risk of insulin resistance.

• Biomolecules & Therapeutics
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• 제7권4호
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• pp.342-346
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• 1999

This study was performed to investigate the effect of cyclosporine (CsA) on glucose tolerance and peripheral insulin sensitivity in normal Sprague-Dawley rats. After daily treament of CsA (10 mg/kg, i.p.) for two weeks, glucose tolerance tests were carried out by the treatment of glucose (Glu, 2 g/kg, i.p.) alone or in conjunction with exogenous insulin (Ins; human regular insulin, 5 U/kg, s.c.) and measured the decrement of area under the time-plasma glucose concentration curve ($AUC_{o\longrightarrow120}$; g.min/ml) by the trapezoidal rule. The rats were divided into three groups (Glu- (Control), Ins+Glu- and CsA+Ins+Glu-, n=7 in each group). The $AUC_{o\longrightarrow120}$ of the CsA+Ins+Glu-group was significantly (p<0.01) lower than that of Glu-group (61.0% of control) and significantly (p<0.05) higher than that of Ins+Glu-group (197.4% of Ins+Glu-). The CsA+Ins+Glu- grou showed higher levels of maximal blood glucose concentration and higher $AUC_{o\longrightarrow120}$ than those of Ins+Glu-group in normal rats. Besides direct pancreatic toxicity of CsA previously reported (Hahn et al., 1972), these results suggest that CsA also make the possibility to induce peripheral insulin insensitivity and glucose intolerance in normal rats.

• Journal of Applied Biological Chemistry
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• 제64권1호
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• pp.89-96
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• 2021

이 연구의 목적은 Caulerpa okamurae 에탄올 추출물(COE)이 제2형 당뇨병 치료의 약물 표적 중 하나인 당 대사 및 인슐린 민감성에 미치는 영향을 평가하는 것이다. COE는 in vitro 실험에서 단백질 티로신 포스타제 1B (PTP1B)와 디펩티딜 펩티데이즈-IV (DPP-IV) 효소 활성을 유의하게 억제시켰다. 또한, COE는 3T3-L1 지방세포와 제브라피쉬에서 당 흡수, 인슐린 수용체 기질(IRS-1) 및 당 수송체(GLUT4) 단백의 발현을 대조군에 비해 유의하게 향상시켰다. L6 근육세포의 덱사메타손(dexamethasone)으로 유도된 인슐린 저항성 모델에서도 COE는 인슐린 신호전달 및 당 흡수 단백의 발현을 효과적으로 증가시켰다. 더불어 인슐린 저항성 지표로 알려진 IRS-1 Ser307의 인산화 활성도 COE 첨가에 의해 유의하게 억제되었다. 그러나 COE는 췌장 베타세포의 인슐린 분비에는 아무런 영향을 미치지 않았다. 결론적으로 COE는 인슐린 표적세포와 제브라피쉬에서 인슐린 신호전달과 당 수송체 GLUT4 단백 발현의 조절을 통해 당 대사 및 인슐린 민감성을 개선시키는 것으로 밝혀졌다.

• Journal of Ginseng Research
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• 제39권4호
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• pp.331-337
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• 2015

Background: The biological actions of various ginseng extracts have been studied for treating obesity and diabetes mellitus. However, few studies have evaluated the effects of fermented Korean Red Ginseng (Panax ginseng Meyer) on metabolic syndrome. The present study evaluated the antiobesity and antidiabetic effects of fermented red ginseng (FRG) on old-aged, obese, leptin-deficient (B6.V-Lepob, "ob/ob") mice. Methods: The animals were divided into three groups and given water containing 0%, 0.5%, and 1.0% FRG for 16 wk. The effect of FRG on ob/ob mice was determined by measuring changes in body weight, levels of blood glucose, serum contents of triglycerides, total cholesterol and free fatty acids, messenger RNA (mRNA) expressions of key factors associated with insulin action, such as insulin receptor (IR), lipoprotein lipase (LPL), glucose transporter 1 and 4 (GLUT1 and GLUT4), peroxisome proliferators-activated receptor gamma ($PPAR-{\gamma}$), and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and in muscle, and histology of the liver and pancreas. Results: FRG-treated mice had decreased body weight and blood glucose levels compared with control ob/ob mice. However, anti-obesity effect of FRG was not evident rather than hypoglycemic effect in old aged ob/ob mice. The hyperlipidemia in control group was attenuated in FRG-treated ob/ob mice. The mRNA expressions of IR, LPL, GLUT1, GLUT4, $PPAR-{\gamma}$, and PEPCK in the liver and in muscle were increased in the FRG-treated groups compared with the control group. Conclusion: These results suggest that FRG may play a vital role in improving insulin sensitivity relative to reducing body weight in old-aged ob/ob mice.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3123-3128
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• 2014

The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the stability of HepG2/IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells.