• Food Science and Biotechnology
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• 제17권6호
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• pp.1146-1150
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• 2008

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.

• The Korean Journal of Physiology and Pharmacology
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• 제25권3호
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• pp.177-187
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• 2021

Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

• BMB Reports
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• 제54권6호
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• pp.323-328
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• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.

• 운동영양학회지
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• 제16권2호
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• pp.85-92
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• 2012

This study was conducted to examine the possibility of Salicornia herbacea L. powder as a functional food beneficially affecting carbohydrate metabolism and antioxidant capacity. Twenty-four, 6-week old, maleSprague-Dawleyrats were classified into three groups: normal diet control (CON), high-fat diet control (HFC) and high fat diet + Salicornia herbacea L. (SHF). Related feed was provided to each group for 4 weeks. Weight gain rate increased most in the HFC rats, and the concentration of glucose was significantly high in both the HFC and SHF groups, compared to the CON group. The SHF group showed a significantly high expression rate of Glut 4 (21.36%), compared to the CON and HFC groups. The glycogen content in muscle was significantly high in both the HFC and SHF groups, compared to the CON group. There were significant differences in the malondialdehydecontent in muscles between the groups, with the content in the CON and HFC groups being significantly higher than the SHF group. All the groups showed a similar tendency to each other in the liver tissue as well. Concerning the expression of Cu,Zn-super oxide dismutase andglutathione peroxidaseproteins, the SHF group was significantly higher than the CON and HFC groups. Overall, the experiment result above implies a possibility that an intake of Salicornia herbacea L. powder can regulate weight by decreasing the weight gain rate, further suggesting its effectiveness as a functional food before exercise by increasing the energy storage capacity and antioxidant capacity.

• BMB Reports
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• 제57권2호
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• pp.92-97
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• 2024

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis.

• Clinical Nutrition Research
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• 제12권3호
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• pp.169-176
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• 2023

Glucose transporter type 1 (GLUT1) deficiency syndrome (DS) is a metabolic brain disorder caused by a deficiency resulting from SLC2A1 gene mutation and is characterized by abnormal brain metabolism and associated metabolic encephalopathy. Reduced glucose supply to the brain leads to brain damage, resulting in delayed neurodevelopment in infancy and symptoms such as eye abnormalities, microcephaly, ataxia, and rigidity. Treatment options for GLUT1 DS include ketogenic diet (KD), pharmacotherapy, and rehabilitation therapy. Of these, KD is an essential and the most important treatment method as it promotes brain neurodevelopment by generating ketone bodies to produce energy. This case is a focused study on intensive KD nutritional intervention for an infant diagnosed with GLUT1 DS at Gangnam Severance Hospital from May 2022 to January 2023. During the initial hospitalization, nutritional intervention was performed to address poor intake via the use of concentrated formula and an attempt was made to introduce complementary feeding. After the second hospitalization and diagnosis of GLUT1 DS, positive effects on the infant's growth and development, nutritional status, and seizure control were achieved with minimal side effects by implementing KD nutritional intervention and adjusting the type and dosage of anticonvulsant medications. In conclusion, for patients with GLUT1 DS, it is important to implement a KD with an appropriate ratio of ketogenic to nonketogenic components to supply adequate energy. Furthermore, individualized and intensive nutritional management is necessary to improve growth, development, and nutritional status.

• Journal of Medicine and Life Science
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• 제21권3호
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• pp.62-71
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• 2024

The incidence of diabetes is continuously increasing worldwide, resulting in a considerable socioeconomic burden. Glycemic control using traditional diabetes medications prevents microvascular complications; however, there is no objective evidence that it prevents macrovascular complications. In the 21st century, concerns have arisen that strict glycemic control and the diabetes drug rosiglitazone might increase mortality. This led the United States Food and Drug Administration to establish guidelines that require that cardiovascular outcome trials (CVOTs) with 3-point major adverse cardiovascular events (3-P MACE) as the primary endpoints be performed for new diabetes drugs. Since then, 20 CVOTs have been reported. Dipeptidyl peptidase 4 inhibitors do not increase the incidence of cardiovascular disease; however, saxagliptin increases the risk of heart failure. Sodium-glucose cotransporter inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) not only have proven cardiovascular safety but also have shown results beyond expectations by reducing the incidence of cardiovascular diseases. Additionally, SGLT2is have been reported to markedly prevent heart failure and kidney disease. The reduction in 3-P MACE by GLP-1RAs was observed only with long-acting agents; long-acting GLP-1RAs also markedly reduced renal endpoints. However, no preventive effect against heart failure was observed with GLP-1RAs. The preventive effects of both drug types against cardiovascular and kidney diseases appear to be independent of glycemic control. In conclusion, based on CVOT results, it is necessary to actively prescribe SGLT2is and GLP-1RAs to prevent cardiovascular disease in patients with diabetes, regardless of glycemic control.

• Journal of Yeungnam Medical Science
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• 제14권1호
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• pp.53-66
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• 1997

인슐린 저항성이란 인슐린의 생물학적 효과가 감소하는 상태를 말하며 당뇨병의 중요한 병리기전이다. 인슐린 저항성은 매우 다양한 특성을 가지고 있으며 유전적인 요인이나 후천적인 요인에 의하여 발생한다. 이제까지 가장 잘 알려진 인슐린 저항성의 유발인자로는 고혈당과 고인슐린증이 있다. 장기간의 고혈당이나 고인슐린증은 가장 중요한 인슐린의 작용조직인 골격근에서 인슐린 수용체의 결합능을 감소시키고 당섭취에 필요한 제 4형 당수송체의 발현을 억제하는 것으로 알려져 있다. 그러나 이들 인자는 모두 골격근에서 당섭취를 증가시키는 것으로서 인슐린 저항성은 말초조직이 세포내로의 과도한 영양소 섭취를 방지하기 위하여 작동시키는 조절기전일 가능성을 생각할 수 있다. 본 연구에서는 단기간의 당섭취 증가가 더 이상의 당섭취를 억제할 수 있는지를 평가하고 그 기전을 규명하고자 흰쥐에서 2시간 동안 다양한 조건으로 당섭취를 유도하고 1 시간의 휴식기간을 가진 후 인슐린 예민도를 측정하고 골격근을 분리하여 인슐린 수용체와 제 4 형 당수송체를 분석하여 당섭취량과 인슐린 감수성과의 상관관계를 규명하고 인슐린 수용체 결합능과 제 4형 당수송체량을 비교하였다. 실험군은 hyperinsulinemic glucose clamp 전에 시행한 당섭취의 조건으로써 5개 군으로 구분하였다. 제 I 군은 대조군으로 생리식염수만 주입하여 기초상태의 인슐린 농도와 혈당을 유지하였으며, 제 II 군은 somatostatin과 포도당을 주입하여 정상 인슐린농도와 고혈당을 유지하였으며, 제 III 군은 포도당을 주입하여 고인슐린증과 고혈당을 유지하였고, 제 IV 군은 인슐린(100 mU/kg/min)과 포도당을 주입하여 초고인슐린증(${\sim}4000{\mu}U/ml$)과 정상혈당(~100 mg/dl)으로 유지하였으며, 그리고 제 V 군은 인슐린과 포도당을 주입하여 초고인슐린증과 고혈당(~200 mg/dl)을 유지하였다. 체중, 공복시 혈당 및 인슐린 농도는 각 군 간에 유의한 차이가 없었다. Hyperinsulinemic euglycemic clamp 전에 주입한 포도당의 총량(gm/kg)은 제 II 군이 $1.88{\pm}0.151$, 제 III 군이 $2.69{\pm}0.239$, 제 IV 군이 $3.54{\pm}0.198$, 그리고 제 V 군이 $4.32{\pm}0.621$이었다. Hyperinsulinemic euglycemic clamp의 평형상태 당제거율(mg/kg min)은 제 I 군이 $16.9{\pm}1.74$, 제 II 군이 $13.5{\pm}0.53$, 제 III 군이 $11.2{\pm}0.52$, 제 IV 군이 $13.2{\pm}0.92$, 그리고 제 V 군이 $10.4{\pm}0.41$로 전체 군 간에 유의한 차이가 있었으며(p<0.001) 각 군간의 비교에서 제 II, III, IV, V 군의 값이 제 I 군에 비하여 유의하게 낮았다 (p<0.05). 전체 실험동물에서 포도당 주입량과 당제거율 사이에 역상관관계 (r=-0.701, p<0.001)를 보였다. 인슐린 수용체 결합과 Western blot으로 분석한 제 4형 당수송체량은 각 군 간에 유의한 차이가 없었다. 이상의 결과로 미루어 단기간의 당섭취 증가가 더이상의 당섭취를 억제할 수 있으나 인슐린 수용체 결합과 제 4형 당수송체의 숫적 감소없이 발생하였다.

• Nutrition Research and Practice
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• 제9권1호
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• pp.22-29
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• 2015

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2-fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ${\beta}$-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ${\beta}$-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.

• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.153-160
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• 2016

The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into five groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of $3^{rd}$ week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefit effects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-$AMPK{\alpha}$1/2.