• 대한수의학회지
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• 제54권1호
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• pp.21-26
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• 2014

Although benfotiamine has various beneficial anti-diabetic effects, the detailed mechanisms underlying the impact of this compound on the insulin signaling pathway are still unclear. In the present study, we evaluated the effects of benfotiamine on the hepatic insulin signaling pathway in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a type 2 diabetes mellitus model. OLETF rats treated with benfotiamine showed decreased body weight gain and reduced adipose tissue weight. In addition, blood glucose levels were lower in OLETF rats treated with benfotiamine. Following treatment with benfotiamine, the levels of Akt phosphorylation (S473/T308) in the OLETF groups increased significantly compared to the OLETF control group so that they were almost identical to the levels observed in the control group. Moreover, benfotiamine restored the phosphorylation levels of both glycogen synthase kinase (GSK)-$3{\alpha}/{\beta}$ (S21, S9) and glycogen synthase (GS; S641) in OLETF rats to nearly the same levels observed in the control group. Overall, these results suggest that benfotiamine can potentially attenuate type 2 diabetes mellitus in OLETF rats by restoring insulin sensitivity through upregulation of Akt phosphorylation and activation of two downstream signaling molecules, GSK-$3{\alpha}/{\beta}$ and GS, thereby reducing blood glucose levels through glycogen synthesis.

• 약학회지
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• 제52권5호
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• pp.345-354
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• 2008

This study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng extract through transcriptomics in C57BL/KsJ db/db mice. The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. At the end of treatment, we measured blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). RGL-treated group lowered the blood glucose and HbA1c levels by 19.6% and 11.4% compared to those in diabetic control group. In addition, plasma adiponectin and leptin levels in RGL-treated groups were increased by 20% and 12%, respectively, compared to those in diabetic control. Morphological analyses of liver, pancreas and epidydimal adipose tissue were done by hematoxylin-eosin staining, and pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. RGL-treated group revealed higher insulin contents and lower glucagon contents compared to diabetic control. To elucidate an action mechanism of Korean red ginseng, DNA microarray analyses were performed in liver and fat tissues, and western blot and RT-PCR were conducted in liver for validation. According to hierarchical clustering and principal component analysis of gene expression Korean red ginseng treated groups were close to metformin treated group. In summary, Korean red ginseng lowered the blood glucose level through protecting destruction of islet cells and shifting glucose metabolism from hepatic glucose production to glucose utilization and improving insulin sensitivity through enhancing plasma adiponectin and leptin levels.

• Journal of Ginseng Research
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• 제44권2호
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• pp.238-246
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• 2020

Background: Dietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear. Methods: This study was conducted to examine the therapeutic effect of GBHT on fat-induced obesity, hepatic steatosis, and insulin resistance in mice. Results: GBHT protected mice against HFD-induced body weight gain, hyperlipidemia, and hyperglycemia compared with mice that were not treated. GBHT inhibited the expansion of adipose tissue and adipocyte hypertrophy. No ectopic fat deposition was found in the livers of HFD mice treated with GBHT. In addition, glucose intolerance and insulin sensitivity in HFD mice was also improved by GBHT. Conclusion: GBHT prevents changes in lipid and carbohydrate metabolism in a HFD mouse model. Our findings provide evidence for the traditional use of GBHT as therapy for the management of metabolic syndrome.

• Nutrition Research and Practice
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• 제15권5호
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• pp.568-578
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• 2021

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 ㎍/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor 𝛄 (PPAR𝛄), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS: The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

• 생명과학회지
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• 제31권1호
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• pp.1-9
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• 2021

본 연구는 갈조류 유래 물질인 후코이단이 인슐린 민감성을 증진시키는지를 규명하기 위하여 3T3-L1 지방세포에서 포도당 흡수에 미치는 후코이단의 영향을 측정하고 그 작용기전을 조사하였다. 후코이단은 지방세포에서 포도당 흡수를 유의하게 증가시켰으며 이는 PM-GLUT4의 발현 증가와 관련이 있음을 관찰하였다. 후코이단은 인슐린 신호전달 경로에서 PI3K의 활성화 및 pIRS1tyr, Akt, PKCλ/ζ의 인산화를 대조군에 비해 유의하게 증가시켰다. 또한, AMPK의 활성화를 나타내는 pAMPK 수준이 유의하게 증가하였다. 이들 PI3K 및 AMPK 활성화는 포도당 수송체인 GLUT4를 세포막으로 이동시켰으며 이로 인하여 PM-GLUT4의 발현이 증가되고 포도당 흡수가 촉진되었다. 후코이단에 의한 PI3K 및 AMPK 경로의 활성화를 증명하기 위해, PI3K 억제제인 Wortmannin과 AMPK의 억제제인 Compound C를 사용하여 이들 처리에 의한 포도당 흡수능과 PM-GLUT4의 발현을 측정한 결과 이들의 발현이 유의하게 저해되었다. 따라서 후코이단은 3T3-L1 지방세포에서 PI3K 및 AMPK 경로를 활성화시킴으로써 인슐린 민감성을 증진하고 포도당 흡수를 촉진시킬 수 있음을 나타내었다.

• Journal of Ginseng Research
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• 제46권4호
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• pp.561-571
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• 2022

Background: Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin. Methods: 3T3-L1 adipocytes and hepatocytes were used to investigate GRb1's action on adiponectin expression and triglyceride (TG) accumulation. Wild type (WT) mice and adiponectin knockout (KO) mice fed high fat diet were treated with GRb1 for 2 weeks. Hepatic fat accumulation and function as well as insulin sensitivity was measured. The activation of AMPK was also detected in the liver and hepatocytes. Results: GRb1 reversed the reduction of adiponectin secretion in adipocytes. The conditioned medium (CM) from adipocytes treated with GRb1 reduced TG accumulation in hepatocytes, which was partly attenuated by the adiponectin antibody. In the KO mice, the GRb1-induced significant decrease of TG content, ALT and AST was blocked by the deletion of adiponectin. The elevations of GRb1-induced insulin sensitivity indicated by OGTT, ITT and HOMA-IR were also weakened in the KO mice. The CM treatment significantly enhanced the phosphorylation of AMPK in hepatocytes, but not GRb1 treatment. Likewise, the phosphorylation of AMPK in liver of the WT mice was increased by GRb1, but not in the KO mice. Conclusions: The up-regulation of adiponectin by GRb1 contributes to the amelioration of liver steatosis and insulin resistance, which further elucidates a new mechanism underlying the beneficial effects of GRb1 on obesity.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.177.2-177.2
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• 2003

Thiazolidinediones (TZDs) are a new class of compound that increase insulin sensitivity in type 2 diabetic patients. Thiazolidinediones (TZDs) act as ligands for a member of the nuclear hormone receptor superfamily, peroxisome proliferator-activated receptor-$\gamma$ (PPAR-$\gamma$), which is highly expressed in fatty tissue and, moreover, has been shown to play an important role in fat cell differentiation. The strong interaction between the antidiabetic activity ofTZDs and their ability to activate PPAR-$\gamma$ suggests that PPAR-$\gamma$, through downstream-regulated genes, mediates the effects of TZDs. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.186.2-186.2
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• 2003

PPARs (peroxisome proliferator activated receptors) are member of nuclear hormone receptors superfamily. Activations of PPARs upon binding with ligands modulate glucose metabolite, differentiation of adipocyte, inflammation response, and so on. Thiazolidinedione analog is one of the potential antidiabetic drug that binds and activates PPAR selectively and enhances insulin sensitivity. In an effort to develop novel and effective antidiabetic thiazolidindione analogs, we have synthesized tetrahydroquinoline and para-substituted benzene-linked thiazolidinedione analogs by coupling reaction of the hydrophobic segments with hydroxybenzylthiazolidinedione.

• 한국식품영양과학회지
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• 제40권11호
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• pp.1537-1543
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• 2011

본 연구는 제2형 당뇨동물모델인 Goto-Kakizaki(GK)랫드에 대한 성게껍질의 항당뇨 효과를 조사하였다. 즉 Wistar 랫드로 구성된 정상군, GK랫드 대조군, GK랫드에 성게껍질을 각각 100 mg/kg 및 200 mg/kg 투여군으로 나누고 매일 1회씩 4주간 경구투여 하여 체중, 혈당, 혈장 인슐린 농도 및 경구당부하 검사를 실시하였다. 그 결과 성게껍질을 투여한 GK랫드의 혈당은 203.8${\pm}$29.8 mg/dL에서 138.5${\pm}$21.2 mg/dL로 유의적으로 감소하였다. 그러나 성게껍질투여에 따른 GK랫드의 혈장 내 인슐린 농도의 변화는 없었다. 경구당부하 검사에서 성게껍질을 투여한 GK랫드는 15~120분에서 대조군보다 더 낮은 혈당으로 나타났다. 또한 췌장의 조직학적 변화는 성게껍질을 투여한 랫드에서 전체적인 췌도세포의 크기나 공포성 변화 및 선방세포의 배열 및 크기가 대조군에 비하여 정상군에 근접한 형태로 나타났다. 따라서 성게껍질은 당뇨모델인 GK 랫드의 혈당을 저하시키고 내당능이나 인슐린저항성을 개선하므로 향후 이를 활용하여 항당뇨 식품 및 원료개발에 활용될 것으로 기대된다.

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.223-229
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• 2019

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR). T2DM is correlated with obesity and most T2DM medications have been developed for enhancing insulin sensitivity. Silk protein fibroin (SPF) from spiders has been suggested as an attractive biomaterial for medical purposes. We generated transgenic rice (TR) expressing SPF and fed it to diabetic $BKS.Cg-m+/+Lepr^{db}$ mice to monitor the changes in blood glucose levels and adipose tissue proteins associated with energy metabolism and insulin signaling. In the present study, the adipocyte size in abdominal fat in TR-SPF-fed mice was remarkably smaller than that of the control. Whereas the adenosine monophosphate-activated protein kinase (AMPK)-activated protein kinase and insulin receptor substrate 1 (IRS1) protein levels were increased in abdominal adipose tissues after TR-SPF feeding, levels of six-transmembrane protein of prostate 2 (STAMP2) proteins decreased. Phosphorylation of AMPK at threonine 172 and IRS1 at serine 307 and tyrosine 632 were both increased in adipose tissues from TR-SPF-fed mice. Increased expression and phosphorylation of IRS1 at both serine 307 and tyrosine 632 in adipose tissues indicated that adipocytes obtained from abdominal fat in TR-SPF-fed mice were more susceptible to insulin signaling than that of the control. STAMP2 protein levels decreased in adipose tissues from TR-SPF-fed mice, indicating that STAMP2 proteins were reducing adipocytes that were undergoing lipolysis. Taken together, this study showed that TR-SPF was effective in reducing blood glucose levels in diabetic mice and that concurrent lipolysis in abdominal adipocytes was associated with alterations of AMPK, IRS1, and STAMP2. Increased IRS1 expression and its phosphorylation by TR-SFP were considered to be particularly important in the induction of lipolysis in adipocytes, as well as in reducing blood glucose levels in this animal model.