• Proceedings of the PSK Conference
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• 2003.10b
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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.

• Journal of Microbiology and Biotechnology
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• v.3 no.2
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• pp.78-85
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• 1993

In order to elucidate the mechanism which regulates the production of cyclodextrin glucanotransferase (CGTase) and to achieve overproduction of CGTase by releasing catabolite (glucose) repression, several catabolite repression resistant mutants were selected from newly screened Bacillus firmus var. alkalophilus H609, after NTG (N-methyl-N -nitro-N-nitrosoguanidine) treatment, using 2-deoxyglucose as a nonmetabolizable analog of catabolite glucose and as a selection marker. Five catabolite repression resistant mutants were selected from about 30, 000 2-deoxyglucose resistant colonies. Relative catabolite repression indices of the selected mutants were in the range of 8~80% assuming 100% for parent strain. The amount of CGTase produced by the mutant strain CR41, which was 250 units/ml, was three times larger than that produced by its parent strain. The mutation seems to have occurred in the regulatory region of CGTase gene and not in the structural region or the glucose transporting system in cell membrane. The enzymatic properties of CGTase excreted from parent and mutant strains were also compared.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.2
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• pp.35-37
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• 2016

Prader-Willi syndrome (PWS) often develops type 2 diabetes mellitus (T2DM) related to severe obesity. The prevalence of T2DM in adults with PWS (7-20%) exceeds greatly the prevalence in the general population (5-7%). It is uncommon for pre-pubertal children with PWS to develop overt diabetes or glucose intolerance. GH therapy and genotype did not influence the development of altered glucose metabolism. It has been assumed that T2DM in PWS develops as a consequence of morbid obesity and concomitant insulin resistance. However recent studies suggest the relationship between morbid obesity and T2DM development is more complex and appears to differ in PWS subjects compared to non-PWS subjects. PWS patients had relatively lower fasting insulin levels and increased adiponectin levels compared with BMI-matched obese control despite of similar levels of leptin. So PWS children may be protected to some extent form of obesity-associated insulin resistance. Although there's no data, it seems logical to approach diabetes management including weight loss and increased exercise, using similar pharmacological agents as with non-PWS obesity-related diabetes such as metformin or thiazolidinedione, with the introduction of insulin as required. On the other hand, several recent T2DM in PWS case reports suggest favorable outcomes using Glucagon-like peptide 1 (GLP-1) analog with regard to ghrelin reduction, control of glucose and appetite, weight loss and pre-prandial insulin secretion. The role of GLP-1 agonist therapy is promising, but has not yet been fully elucidated.

• YAKHAK HOEJI
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• v.49 no.1
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• pp.68-73
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• 2005

Epi-xanthatin analogs containing hydrophilic substituents such as carboxylic acid, alcohol, morpholine, amino acid, and glucose derivatives were synthesized and their in vitro cytotoxicity and in vivo antitumor activity were evaluated. The target compounds were generally cytotoxic against tumor cell lines of human origin with $ED_{50}$ values of $0.1{\sim}30{\mu}g/ml$, except the highly hydrophilic analog 6 containing aspartic acid. Contrary to the potent cytotoxicity weakly hydrophilic analogs 2 and 8 were not active in vivo, or even toxic to the test animals. As a result, hydrophilic analog of epi-xanthatin did not show in vitro cytotoxicity and hydrophobic analogs did not show in vivo antitumor activity, thus it is presumed that amphiphilic analogs or those with medium hydrophilicity would exhibit the antitumor potency in vivo.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.9
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• pp.1316-1321
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• 2012

Adipokines, adipocyte-derived protein, have important roles in various kinds of physiology including energy homeostasis. Chemerin, one of adipocyte-derived adipokines, is highly expressed in differentiated adipocytes and is known to induce macrophage chemotaxis and glucose intolerance. The objective of the present study was to investigate the changes of chemerin and the chemokine-like-receptor 1 (CMKLR1) gene expression levels during differentiation of the bovine adipocyte and in differentiated adipocytes treated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), adiponectin, leptin, and chemerin (peptide analog). The expression levels of the chemerin gene increased at d 6 and 12 of the differentiation period accompanied by increased cytoplasm lipid droplets. From d 6 onward, peroxisome proliferator-activated receptor-${\gamma}2$ (PPAR-${\gamma}2$) gene expression levels were significantly higher than that of d 0 and 3. In contrast, CMKLR1 expression levels decreased at the end of the differentiation period. In fully differentiated adipocytes (i.e. at d 12), the treatment of TNF-${\alpha}$ and adiponectin upregulated both chemerin and CMKLR1 gene expression levels, although leptin did not show such effects. Moreover, chemerin analog treatment was shown to upregulate chemerin gene expression levels regardless of doses. These results suggest that the expression of chemerin in bovine adipocyte might be regulated by chemerin itself and other adipokines, which indicates its possible role in modulating the adipokine secretions in adipose tissues.

• Journal of Microbiology and Biotechnology
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• v.17 no.6
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• pp.1002-1009
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• 2007

A rapid, convenient homogeneous competitive enzyme immunoassay for estimating the amount of fenthion is described. The assay utilizes glucose-6-phosphate dehydrogenase-hapten conjugates that are inhibited in solution by antibodies obtained from bovine serum albumin-hapten conjugates. In order to investigate the effects of bridging group recognition on the sensitivity of dose response characteristics, the bridging groups of varying alkyl chain length were attached at the phosphate position of fenthion. Among the antibodies used, the one obtained from the use of hapten (fenthion analog) with the same bridging group structure that was used in preparing the enzyme-fenthion conjugates showed maximum inhibition (up to 51.8%) in the absence of fenthion. In the presence of fenthion, the activity of the enzyme-hapten conjugate is regained in an amount proportional to the fenthion concentration. Under the optimized condition, the $ED_{50}$ value for fenthion was $0.809{\mu}g/ml$. The assay developed in this study is a rapid effective screening method for fenthion prior to precise analysis.

• Preventive Nutrition and Food Science
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• v.13 no.3
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• pp.182-189
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• 2008

In this study, the effect of pH on the antioxidative activities of melanoidins formed as a result of the reaction between sugars, glucose (Glc) or fructose (Fru), and amino acids, L-asparagine (L-Asn) and D-asparagine (D-Asn) are examined. For this purpose, antioxidative activities were evaluated on the basis of reducing power, including ferric reducing/antioxidant power (FRAP) and free radical scavenging activity includes 1,1-diphenyl-2-picryl- hydrazil (DPPH) and 2,2'-azinobis(3-ethylbenothiazoline-6-sulfonic acid) diammonium salt (ABTS) and ferrous ion chelating activity. Ethylene diamine tetraacetate (EDTA) and trolox, a water-soluble analog of tocopherol, were used as reference antioxidant compounds. The antioxidative activities of the melanoidins at a pH of 7.0 were greater than those with a pHs of 4.0 and pH 10.0. Especially, it was found that the melanoidins formed from D-isomers are more effective antioxidants in different in vitro assays. The reducing power and chelating activity of the melanoidins formed from the Fru systems were higher than those of the melanoidins formed from the Glc systems. However, the ABTS radical scavenging activity of the melanoidins formed from the Glc systems were higher than those of the melanoidins formed from the Fru systems. In particular, the DPPH radical scavenging activity and the FRAP of the melanoidins showed different antioxidative activities according to pH level.

• Toxicological Research
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• v.24 no.4
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• pp.245-251
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• 2008

Dietary restriction (DR) is the most efficacious intervention for retarding the deleterious effects of aging. DR increases longevity, decreases the occurrence and severity of age-related diseases, and retards the physiological decline associated with aging. The beneficial effects of DR have been mostly studied in non-neuronal tissues. However, several studies have showed that DR attenuate neuronal loss after several different insults including exposure to kainate, ischemia, and MPTP. Moreover, administration of the non-metabolizable glucose analog 2-deoxy-D-glucose (2DG) could mimic the neuroprotective effect of DR in rodent, presumably by limiting glucose availability at the cellular level. Based on the studies of chemically induced DR, it has been proposed that the mechanism whereby DR and 2DG protect neurons is largely mediated by stress response proteins such as HSP70 and GRP78 which are increased in neurons of rats and mice fed a DR regimen. In addition, DR, as mild metabolic stress, could lead to the increased activity in neuronal circuits and thus induce expression of neurotrophic factors. Interestingly, such increased neuronal activities also enhance neurogenesis in the brains of adult rodents. In this review, we focus on what is known regarding molecular mechanisms of the protective role of DR in neurodegenerative diseases and aging process. Also, we propose that DR is a mild cellular stress that stimulates production of neurotrophic factors, which are major regulators of neuronal survival, as well as neurogenesis in adult brain.

• Journal of Veterinary Science
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• v.22 no.4
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• pp.55.1-55.17
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• 2021

Background: Naringenin and its glycoside naringin are well known citrus flavonoids with several therapeutic benefits. Although the anti-adipogenic effects of naringenin and naringin have been reported previously, the detailed mechanism underlying their anti-adipogenesis effects is poorly understood. Objectives: This study examined the anti-adipogenic effects of naringenin and naringin by determining differential gene expression patterns in these flavonoids-treated 3T3-L1 adipocytes. Methods: Lipid accumulation and triglyceride (TG) content were determined by Oil red O staining and TG assay. Glucose uptake was measured using a 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose fluorescent d-glucose analog. The phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl Co-A carboxylase (ACC) were observed via Western blot analysis. Differential gene expressions in 3T3-L1 adipocytes were evaluated via RNA sequencing analysis. Results: Naringenin and naringin inhibited both lipid accumulation and TG content, increased phosphorylation levels of both AMPK and ACC and decreased the expression level of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in 3T3-L1 adipocytes. RNA sequencing analysis revealed that 32 up-regulated (> 2-fold) and 17 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Scd1, Mogat1, Dgat, Lipin1, Cpt1a, and Lepr, were normalized to the control level in naringenin-treated adipocytes. In addition, 25 up-regulated (> 2-fold) and 25 down-regulated (< 0.6-fold) genes related to lipid metabolism, including Acaca, Fasn, Fabp5, Scd1, Srebf1, Hmgcs1, Cpt1c, Lepr, and Lrp1, were normalized to the control level by naringin. Conclusions: The results indicate that naringenin and naringin have anti-adipogenic potentials that are achieved by normalizing the expression levels of lipid metabolism-related genes that were perturbed in differentiated 3T3-L1 cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.117-117
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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 potential antidiabetic drug that binds and activates PPARν selectively and enhances insulin sensitivity. In an effort to develop novel and effective antidiabetic thiazolidindione analogs, syntheses of benzoxazole and benzothiazole-linked thiazolidinedione analogs were performed via coupling reaction of benzoxazolylalkylaminoethanol with hydroxybenzylthiazolidinedione to develop novel and effective antidiabetic thiazolidindiones. All compounds were evaluated their biological potency by PPARν transactivation assay and revealed the similar potency with Troglitazone. However, lengthening of N-alkyl substituent did not seem to be beneficial for the activity.