• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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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.

• Journal of Medicine and Life Science
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• v.21 no.3
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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 the Korea Academia-Industrial cooperation Society
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• v.10 no.7
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• pp.1766-1772
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• 2009

In this study, we are interested in comparing the protein profiles of acid-shocked and control cells of S. mutans isolated from Korean children with caries. The results of 2D gel electrophoresis showed that twelve proteins are up-regulated when the cells were grown under 20 mM lactic acid stress in the exponential phase. Up-proteins under acid stress were estimated a major key of the survival and proliferation of S. mutans in low pH environments. These proteins are estimated generally associated with three biochemical pathways: glycolysis, alternative acid production and branched-chain amino acid biosynthesis.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.8
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• pp.1189-1196
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• 2013

Adipose tissue development and function play a critical role in the regulation of energy balance, lipid metabolism, and the pathophysiology of metabolic syndromes. Although the effect of zinc ascorbate supplementation in diabetes or glycemic control is known in humans, the underlying mechanism is not well described. Here, we investigated the effect of a zinc-chelated vitamin C (ZnC) compound on the adipogenic differentiation of 3T3-L1 preadipocytes. Treatment with ZnC for 8 d significantly promoted adipogenesis, which was characterized by increased glycerol-3-phosphate dehydrogenase activity and intracellular lipid accumulation in 3T3-L1 cells. Meanwhile, ZnC induced a pronounced up-regulation of the expression of glucose transporter type 4 (GLUT4) and the adipocyte-specific gene adipocyte protein 2 (aP2). Analysis of mRNA and protein levels further showed that ZnC increased the sequential expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha (C/$EBP{\alpha}$), the key transcription factors of adipogenesis. These results indicate that ZnC could promote adipogenesis through $PPAR{\gamma}$ and C/$EBP{\alpha}$, which act synergistically for the expression of aP2 and GLUT4, leading to the generation of insulin-responsive adipocytes and can thereby be useful as a novel therapeutic agent for the management of diabetes and related metabolic disorders.

• Genomics & Informatics
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• v.7 no.2
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• pp.53-56
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• 2009

Recent evidence has strongly suggested that the CAP/TC10 pathway is involved in the trafficking, docking, and fusion of vesicles containing the insulin-responsive glucose transporter Glut4 to the plasma membrane. However, little is known about how the genes employed in the CAP/TC10 pathway are associated with the development of type 2 diabetes mellitus. In this study, we sequenced 4 genes of the CAP/TC10 pathway [SORBS1, CBL, CRK, and RHOQ] in 24 individuals to identify genetic variations in these loci. A total of 48 sequence variants were identified, including 23 novel variations. To investigate the possible association with type 2 diabetes mellitus, 3 single nucleotide polymorphisms from SORBS1, 3 from CBL, and 4 from RHOQ were genotyped in 1122 Korean type 2 diabetic patients and 1138 nondiabetic controls. Using logistic regression analysis, 1 significant association between SNP rs1376405 in RHOQ and type 2 diabetes mellitus [OR = 8.714 (C.I. 1.714-44.29), p = 0.009] was found in the recessive model. Our data demonstrate a positive association of the RHOQ gene in the CAP/TC10 pathway with T2DM in the Korean population.

• Microbiology and Biotechnology Letters
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• v.44 no.4
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• pp.563-570
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• 2016

Two Streptomyces griseus strains, a wild-type strain and an A-factor-dependent transcriptional activator mutant strain harboring multiple copies of a gene, dasA, that encodes a substrate-binding protein of the ATP-binding cassette transporter, showed severe ectopic sporulation of young substrate hyphae in response to glucose. The effect of dasA overexpression on the ectopic sporulation of Streptomyces strains was evaluated by comparing the transcriptomes of the strain harboring multiple copies of dasA and a strain harboring empty vector. By DNA microarray, 4 genes (SGR794, SGR2469, SGR3656, and SGR3657) and 3 clusters (SGR795-797, SGR2377-2378, and SGR6997-6998) were differentially expressed by more than 2-fold in S. griseus strains harboring dasA. The DNA microarray result was validated by low-resolution S1 nuclease mapping.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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• pp.651-661
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• 2020

Objective: We hypothesized that Cr source can alter adipogenic-related transcriptional regulations and cell signaling. Therefore, the objective of the study was to evaluate the biological effects of chromium acetate (CrAc) on bovine intramuscular (IM) and subcutaneous (SC) adipose cells. Methods: Bovine preadipocytes isolated from two different adipose tissue depots; IM and SC were used to evaluate the effect of CrAc treatment during differentiation on adipogenic gene expression. Adipocytes were incubated with various doses of CrAc: 0 (differentiation media only, control), 0.1, 1, and 10 μM. Cells were harvested and then analyzed by real-time quantitative polymerase chain reaction in order to measure the quantity of adenosine monophosphate-activated protein kinase-α (AMPK-α), CCAAT enhancer binding protein-β (C/EBPβ), G protein-coupled receptor 41 (GPR41), GPR43, peroxisome proliferator-activated receptor-γ (PPARγ), and stearoyl CoA desaturase (SCD) mRNA relative to ribosomal protein subunit 9 (RPS9). The ratio of phosphorylated-AMPK (pAMPK) to AMPK was determined using a western blot technique in order to determine changing concentration. Results: The high dose (10 μM) of CrAc increased C/EBPβ, in both IM (p = 0.02) and SC (p = 0.02). Expression of PPARγ was upregulated by 10 μM of CrAc in IM but not in SC. Expression of SCD was also increased in both IM and SC with 10 μM of CrAc treatment. Addition of CrAc did not alter gene expression of glucose transporter 4, GPR41, or GPR43 in both IM and SC adipocytes. Addition of CrAc, resulted in a decreased pAMPKα to AMPKα ration (p<0.01) in IM. Conclusion: These data may indicate that Cr source may influence lipid filling in IM adipocytes via inhibitory action of AMPK phosphorylation and upregulating expression of adipogenic genes.

• Journal of Animal Science and Technology
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• v.63 no.6
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• pp.1397-1410
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• 2021

The present study was designed to determine the influence of all-trans retinoic acid (ATRA) on adipogenesis-related gene regulation in bovine intramuscular (IM) and subcutaneous (SC) adipose cells during differentiation. Bovine IM and SC adipocytes were isolated from three 19-mo-old, crossbred steers. Adipogenic differentiation was induced upon cultured IM and SC preadipocytes with various doses (0, 0.001, 0.01, 0.1, 1 µM) of ATRA. After 96 h of incubation, cells were harvested and used to measure the gene expression of CCAAT/Enhancer binding protein β (C/EBPβ), peroxisome proliferator-activated receptor (PPAR) γ, glucose transporter 4 (GLUT4), stearoyl CoA desaturase (SCD), and Smad transcription factor 3 (Smad3) relative to the quantity of ribosomal protein subunit 9 (RPS 9). Retinoic acid receptor (RAR) antagonist also tested to identify the effect of ATRA on PPARγ -RAR related gene expression in IM cells. The addition of ATRA to bovine IM decreased (p < 0.05) expression of PPARγ. The expression of PPARγ was also tended to be downregulated (p < 0.1) in high levels (10 µM) of ATRA treatment in SC cells. The treatment of RAR antagonist increased the expression of PPARγ in IM cells. Expression of C/EBPβ decreased (p < 0.05) in SC, but no change was observed in IM (p > 0.05). Increasing levels of ATRA may block adipogenic differentiation via transcriptional regulation of PPARγ. The efficacy of ATRA treatment in adipose cells may vary depending on the location.

• Journal of Life Science
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• v.22 no.5
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• pp.634-641
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• 2012

It was reported that the novel compounds (LP9M80-H) of $Liriope$ $platyphylla$ regulate glucose transporter (Glut) biosynthesis by activating the insulin-signaling pathway in the liver and brain of ICR mice. To investigate the therapeutic effects of LP9M80-H on the pathology of diabetes and obesity, alterations of key factors related to symptoms were analyzed in the Otsuka Long Evans Tokushima Fatty (OLETF) rats treated with LP9M80-H for 2 weeks. The abdominal fat masses in the LP9M80-H-treated group were lower than the vehicle-treated group, although there was no difference in body weight between the two groups. Additionally, when compared to the vehicle-treated group, LP9M80-H treatment induced a significant decrease in glucose levels and an increase in the insulin concentration in the blood of OLETF rats. A high level of insulin protein was also detected in pancreatic ${\beta}$ cells of LP9M80-H-treated OLETF rats. A significant reduction in the concentration of lipids and adiponectin was detected only in LP9M80-H-treated OLETF rats. Furthermore, the expression of insulin receptor ${\beta}$ and the insulin receptor substrate (IRS) was dramatically decreased in LP9M80-H-treated OLETF rats compared to the vehicle-treated group. Of the glucose transporters located downstream of the insulin-signaling pathway, glucose transporters (Glut) -2 and -3 were significantly decreased in LP9M80-H-treated OLETF rats, while the level of Glut-4 was maintained under all conditions. Therefore, these results suggest that LP9M80-H may contribute to relieving symptoms of diabetes and obesity through glucose homeostasis and regulation of lipid concentration.

• Journal of Life Science
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• v.33 no.11
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• pp.859-867
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• 2023

Lupeol is a type of pentacyclic triterpene that has been reported to have therapeutic effects for treating many diseases; however, its effect on insulin resistance is unclear clear. This study examined the inhibitory effect of lupeol on the serine phosphorylation of insulin receptor substrate-1 in insulin resistance-induced 3T3-L1 adipocytes. 3T3-L1 cells were cultured and treated with tumor necrosis factor-α (TNF-α) for 24 hours to induce insulin resistance. Cells treated with different concentrations of lupeol (15 μM or 30 μM) or 100 nM of rosiglitazone were incubated. Then, lysed cells underwent western blotting. Lupeol exhibited a positive effect on the negative regulator of insulin signaling and inflammation-activated protein kinase caused by TNF-α in adipocytes. Lupeol inhibited the activation of protein tyrosine phosphatase-1B (PTP-1B)-a negative regulator of insulin signaling-and c-Jun N-terminal kinase (JNK); it was also an inhibitor of nuclear factor kappa-B kinase (IKK) and inflammation-activated protein kinases. In addition, Lupeol downregulated serine phosphorylation and upregulated tyrosine phosphorylation in insulin receptor substrate-1. Then, the downregulated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway was activated, the translocation of glucose transporter type 4 was stimulated to the cell membrane, and intracellular glucose uptake increased in the insulin resistance-induced 3T3-L1 adipocytes. Lupeol may improve TNF-α-induced insulin resistance by downregulating the serine phosphorylation of insulin receptor substrate 1 by inhibiting negative regulators of insulin signaling and inflammation-activated protein kinases in 3T3-L1 adipocytes.