• Applied Biological Chemistry
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• v.45 no.1
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• pp.42-46
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• 2002

Effects of the water extract from Kalopanax pictus NAKAI on insulin-like action and glucose uptake in 3T3-L1 cells were investigated. The bark of K. pictus NAKAI was treated with hot water and the extract was freeze-dried. Total extract of K. pictus NAKAI was fractionated into 6 fractions with increasing gradients from 0 to 100% MeOH on Amberlite XDA-4. Treatment of 3T3-L1 fibroblasts with 1 ${\mu}g/ml$ and 10 ${\mu}g/ml$ of K. pictus NAKAI total extracts significantly increased the differentiation of the cells. When co-treated with inducers such a dexamethasone, 1-methyl-3-isobutylxanthine and insulin, the differentiation was increased at 1 ${\mu}g/ml$ of total extract, but not at 10 ${\mu}g/ml$. In 3T3-L1 adipocytes, glucose uptake was increased by 3.3 times with addition of 0.3 and 3 ${\mu}g/ml$ of Fr. 1 (0-10% MeOH) and Fr. 3 (30% MeOH) at 3 ng/ml insulin. In conclusion, K. pictus NAKAI contains such compounds that play a role of insulin-like action and insulin sensitizer.

• Journal of Applied Biological Chemistry
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• v.64 no.1
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• pp.89-96
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• 2021

The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.

• Applied Chemistry for Engineering
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• v.1 no.2
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• pp.107-115
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• 1990

New insulin-releasing system on the basis of the redox reaction of glucose was synthesized by immobilizing insulin through a disulfide bond(5, 5'-dithiobis(2-nitrobenzoic acid) to polymer membrane(poly(methyl methacrylate)) and enzyme(glucose oxidase). The disulfide bonds were cleaved upon oxidation of glucose with glucose dehydrogenase and glucose oxidase, releasing insulin from the membrane and enzyme. Sensitivity to glucose concentration was enhanced by coimmobilization of enzyme cofactors(nicotinamide adenin dinucleotide and flavin adenin dinucleotide) acting as electron mediator(for the membrane device), and further enhanced by direct immobilization of insulin on glucose oxidase(for the protein device). Both systems were specific to glucose, and the released insulin was indistinguishable from native insulin. The biological activity of released insulin was 81% of native insulin.

• Food Science and Industry
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• v.40 no.2
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• pp.46-58
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• 2007

제2형 당뇨병은 대사성 질환으로 간, 근육 그리고 지방 조직 세포에서 인슐린 작용의 장애로 나타나는 인슐린 저항성으로 혈당의 이용이 감소하여 혈당이 높아짐에도 불구하고 췌장의 베타세포에서 인슐린 분비가 충분하지 못할 때 유발된다. 서구에서는 비만 등으로 인해 인슐린 저항성이 증가하면 인슐린 분비가 높은 고인슐린혈증을 나타내어 당뇨병으로의 진전은 늦다. 하지만 우리나라를 비롯한 아시아의 사람들은 인슐린 저항성이 증가할 때 인슐린 분비가 충분치 못해 혈청 인슐린 농도가 정상인과 비슷하거나 더 낮은 상태에서 당뇨병으로 진전된다. 이러한 차이는 우리나라를 비롯한 아시아 사람들에게서 제2형 당뇨병의 발생이 급격하게 증가할 것이라는 보고되었다. 결국 당뇨병은 간, 근육 및 지방조직에서의 인슐린 작용의 장애와 췌장의 베타세포에서 인슐린 분비의 부족의 복합적인 장애에 의해서 나타나고 이것은 공통적으로 각 조직에서의 인슐린/insulin growth factor (IGF)-1 신호전달의 장애와 관련이 있다. 베타세포에서의 인슐린분비 자체는 인슐린/IGF-1 신호전달과 관계가 없지만 간접적으로 관련이 있다. 인슐린 분비능은 베타세포의 증식과 생존에 의한 베타세포의 양과 밀접한 관련이 있는데 인슐린/IGF-1 신호전달은 베타세포의 증식과 생존을 조절한다. 그러므로 혈당 조절에 관여하는 기능성 식품은 인슐린 작용을 향상시키는 인슐린 민감성 특성을 가지거나, 혈당이 높아질 때 인슐린 분비를 촉진시키는 insulinotropic 작용을 하는 성질을 가지고 있어야 하겠다. 전자의 대표적인 약은 1999년에 미국 FDA에서 승인 받은 peroxisome proliferator-activated receptor $(PPAR)-{\gamma}$ agonist 인 thiazolidinedione 계통의 약물인 troglitazone, pioglitazone, rosiglitazone 등이 있고, 후자는 2007년에 승인 받은 Exenatide는 glucagon like peptide (GLP)-1 agonist이다. 이 두 가지 약은 모두 자연계에 존재하는 동식물에서 유래된 것으로 식품에도 많이 다양한 종류의 인슐린 민감성 물질이나 insulinotropic 작용을 하는 물질이 함유되어 있을 것이다. 이러한 기능 이외에 혈당조절 약이나 식품으로 사용되는 것은 탄수화물의 소화를 방해하는 것으로 탄수화물 소화효소인 a-amylase 또는 maltase의 활성을 억제하여 식후 혈당의 급격한 상승을 방지하는 것이 있다. 우리나라 사람들은 탄수화물의 섭취가 너무 많아서 실제로 이러한 식품이나 약의 효능이 높지 않을 것이다. 혈당을 조절하는 기능성 식품은 이 세 가지 효능 중 일부를 가지고 있는 것이 될 수 있다. 이러한 기능을 스크리닝하기 위해서 3가지 단계를 거쳐야 한다. 먼저 시험관에서 또는 세포 실험을 통해서 앞서 언급한 3가지 기능을 가지고 있는 지 여부를 각각 조사한다. 이중에서 효과가 있는 것은 당뇨 동물 모델을 사용하여 in vivo에서 혈당 강하기능과 혈당 강하기전을 조사하는 실험을 한다. 효과가 있는 식품이 우리가 전통적으로 식품으로 섭취해 왔다면 독성 검사를 거쳐야 할 필요가 없지만 한약재이거나 특수 식품의 경우에는 in vivo 실험 전에 GLP 기관에서 반드시 독성 실험을 거쳐 독성 유무를 확인할 필요가 있다. 동물 실험에서 효과적인 것은 인체 실험을 거쳐 혈당 조절 기능성 식품으로 식약청에서 허가를 받을 수 있겠다. 결론적으로 식품에는 항당뇨 특성을 가진 물질들이 함유되어 있는 것들이 상당히 많다. 혈당 조절기능이 있는 기능성 식품으로 개발할 때 고려해야 할 것은 1) 그 양이 혈당 강하 기능성 식품으로 지정받을 수 있을 정도로 충분히 함유되어 있느냐, 2) 혈당을 강하시키는 기전이 단순히 당의 배설을 촉진시켜서 혈당을 저하시키는 것이 아니라, 인슐린 작용을 촉진시키거나, 포도당 자극에 의한 인슐린 분비를 촉진시키거나 탄수화물의 소화 흡수를 억제시킴으로 혈당을 강하시키는 지 등을 파악하는 것이다. 이러한 조건을 만족시키는 식품은 지속적으로 섭취할 때 당뇨병을 예방하거나 진전을 지연시킬 수 있는 혈당조절기능이 있는 기능성 식품으로 개발 가능성이 있겠다.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.6
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• pp.951-957
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• 2004

Hypoglycemic effect of Prunus mume (PM) extract containing in Sangjinyangheul-tang and Hwangkeumtang, one of the diabetic herbal medicines, was determined by investigating insulin-like action, insulin sensitizing action and a-glucoamylase suppressing action. Insulin-like activity of 3T3-L1 fibroblast was not shown with the treatment of PM methanol extracts. However, treatment with 20% or 40% PM methanol extracts and differentiation inducers significantly decreased the differentiation of 3T3-L1 fibroblasts to adipocytes. A significant insulin sensitizing activity was observed in 3T3-L1 adipocytes, giving PM extracts (60%, 80% and 100%) with 1 ng/mL insulin to reach glucose uptake level increased by 50 ng/mL of insulin alone. In addition, 20% and 40% methanol extracts of PM suppressed the a-glucoamylase activity by 30% in vitro. However, there was no significant differences in the peak of serum glucose levels and area under the curve in Sprague Dawley male rats treated with PM ethanol extract or cellulose and 2 g maltose or dextrin/kg body weight. These data suggested that PM extracts contain effective insulin sensitizing compounds, lipid synthesis suppressing compounds and possibly a-glucoamylase suppressing compounds. Therefore, PM extracts are beneficial for anti-diabetic treatment in obese diabetic patients.

• Korean Journal of Food Science and Technology
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• v.39 no.6
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• pp.701-707
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• 2007

Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.

• The Journal of the Korea Contents Association
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• v.9 no.4
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• pp.340-346
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• 2009

Lithium has only a minimal effect on basal glucose transport activity, instead that lithium markedly increased the sensitivity of glucose transport to insulin by increasing in insulin induced glucose transport activity. And Lithium increases in insulin responsiveness as well. Previous studies has reported this enhancement of lithium to stimulate the glucose transport process is not only limited to insulin, it also induce the increases in the sensitivity of glucose transport by submaximal contractile activity. The preliminary study, however, leads that Lithium possibly improves the responsiveness of glucose transport with maximal muscle contraction. In this study, we investigated the effect of Lithium on contraction for the maximal glucose transport. For the purpose of this study, Epitrochlearis muscles of SD rat were isolated and treated Lithium with electric contraction and/or insulin to activate the maximal glucose transport. The results support that Lithium improves the responsiveness of glucose transport through potentiates contraction and/or insulin induced-glucose uptake in muscle. Consequently Lithium treated with muscle contraction and insulin has the important potential to improve the insulin resistance and diabetes.

• Applied Biological Chemistry
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• v.47 no.2
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• pp.258-264
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• 2004

Hypoglycemic effect of Schizandrae Fructus (SF) extract containing in Okchun-san was determined on 3T3-L1 fibroblasts and adipocytes by investigating insulin-like activity, insulin sensitizing activity and ${\alpha}-glucoamylase$ suppressing activity. SF were extracted by using 70% ethanol followed by XAD-4 column chromatography with a mixture solvent of methanol and water, and the fractional extractions were utilized for assaying hypoglycemic effect. No inhibition of ${\alpha}-glucoamylase$ activity of SF was observed. Insulin-like activity 3T3-L1 adipocytes was not shown by SF. A significant insulin sensitizing activity of SF extractions was observed in 3T3-L1 adipocytes, giving SF extractions with 1 ng/ml insulin to reach glucose uptake level increased by 50 ng/ml of insulin alone. When cells were treated with SF (Fr. 4 or 5) plus 1 ng/ml insulin, glucose uptake was increased more than seven times as compared to 1 ng/ml of insulin alone, suggesting that SF extracts increased GLUT4 content by enhancing insulin signaling. These data suggest that SF extracts (especially Fr. 4 and 5) contains an effective insulin sensitizing compounds for hypoglycemic activity in 3T3-L1 adipocytes.

• Korean Journal of Food Science and Technology
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• v.36 no.3
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• pp.472-477
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• 2004

Hypoglycemie effect of Moutan Radicis Cortex (MRC) extract contained in Yukmijihuang-hwan was determined by investigating insulin-sensitizing and ${\alpha}-glucoamylase-suppressing$ actions. MRC was extracted with 70% ethanol, fractionated by XAD-4 column chromatography with mixture solvent of methanol and water, and utilized for hypoglycemic effect assay. Significant insulin sensitizing activities of MRC extracts were observed in 3T3-L1 adipocytes, giving MRC extracts with 1 ng/mL insulin reach glucose uptake level increased by 50 ng/mL of insulin alone. MRC methanol extracts of 20, 40, 60, and 80% suppressed ${\alpha}-glucoamylase$ activity in vitro. Peak serum glucose levels and area under curve were lower in Sprague Dawley male rats treated with MRC ethanol extract than those treated with cellulose in oral glucose tolerance test using 2 g dextrin/kg body weight. These data suggest MRC extracts contain effective insulin -sensitizing and ${\alpha}-glucoamylase-suppressing$ compounds for hypoglycemic activity.

• Korean Journal of Food Science and Technology
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• v.39 no.3
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• pp.330-335
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• 2007

This study was performed to investigate the anti-diabetic mechanism of crude polysaccharides isolated from the fruiting bodies of Grifola frondosa. We treated 3T3-L1 adipocyte cells to observe whether the crude polysaccharides isolated from Grifola frondosa would stimulate insulin sensitivity. Significant insulin sensitizing activity was observed in the 3T3-L1 adipocytes, and giving the crude polysaccharide of Grifola frondosa with 1 nM of insulin caused glucose uptake to increase to a similar level as giving 50 nM of insulin alone. To confirm the mechanism for the anti-diabetic effect of the crude polysaccharides, we performed further examinations within $KK-A^{y}$ mice, an animal model of type 2 diabetes. The crude polysaccharides reduced blood glucose levels in the $KK-A^{y}$ mice for 2 weeks after feeding, and also significantly lowered plasma insulin levels. These results suggest that the anti-diabetic mechanism of the crude polysaccharide of Grifola frondosa is related to the enhancement of insulin sensitivity.