• Nutrition Research and Practice
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• v.10 no.5
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• pp.507-515
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• 2016

BACKGROUND/OBJECTIVES: This study was designed to investigate whether Gynura procumbens extract (GPE) can improve insulin sensitivity and suppress hepatic glucose production in an animal model of type 2 diabetes. MATERIALS/METHODS: C57BL/Ksj-db/db mice were divided into 3 groups, a regular diet (control), GPE, and rosiglitazone groups (0.005 g/100 g diet) and fed for 6 weeks. RESULTS: Mice supplemented with GPE showed significantly lower blood levels of glucose and glycosylated hemoglobin than diabetic control mice. Glucose and insulin tolerance test also showed the positive effect of GPE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in mice supplemented with GPE than in the diabetic control mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and PM-glucose transporter type 4 increased in mice supplemented with GPE when compared to that of the diabetic control mice. GPE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. CONCLUSIONS: These findings demonstrate that GPE might improve insulin sensitivity and inhibit gluconeogenesis in the liver.

• Natural Product Sciences
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• v.20 no.1
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• pp.1-6
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• 2014

P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

• Journal of Microbiology and Biotechnology
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• v.16 no.5
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• pp.795-798
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• 2006

The phosphoenolpyruvate-dependent carbohydrate phosphotransferase system (PTS) is responsible for the simultaneous transfer and phosphorylation of various carbon sources in Escherichia coli. The ptsG gene encoding the enzyme $IICB^{Glc}$, the membrane component of the glucose-specific PTS, is repressed by Mlc and activated by the CRP cAMP complex; various other factors, such as Fis, FruR, and ArcA, are also known to be involved in ptsG regulation. Thus, in an attempt to discover a novel gene affecting the regulation of ptsG, a mutant with a decreased ptsG transcription in the presence of glucose compared with the wild-type strain was screened using transposon random mutagenesis. The mutant was found to have a transposon insertion in yhjV, a putative gene encoding a transporter protein whose function is yet unknown.

• Journal of Microbiology and Biotechnology
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• v.26 no.4
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• pp.710-716
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• 2016

Gamma-aminobutyric acid (GABA) is a non-protein amino acid, which is an important inhibitor of neurotransmission in the human brain. GABA is also used as the precursor of biopolymer Nylon-4 production. In this study, the carbon flux from the tricarboxylic acid cycle was directed to the GABA shunt pathway for the production of GABA from glucose. The GABA shunt enzymes succinate-semialdehyde dehydrogenase (GabD) and GABA aminotransferase (GabT) were co-localized along with the GABA transporter (GadC) by using a synthetic scaffold complex. The co-localized enzyme scaffold complex produced 0.71 g/l of GABA from 10 g/l of glucose. Inactivation of competing metabolic pathways in mutant E. coli strains XBM1 and XBM6 increased GABA production 13% to reach 0.80 g/l GABA by the enzymes co-localized and expressed in the mutant strains. The recombinant E. coli system developed in this study demonstrated the possibility of the pathway of the GABA shunt as a novel GABA production pathway.

• YAKHAK HOEJI
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• v.59 no.1
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• pp.29-39
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• 2015

In recent years, physiologically based pharmacokinetic (PBPK) modeling has been widely used in pharmaceutical industries as well as regulatory health authorities for drug discovery and development. Several application areas of PBPK have been introduced so far including drug-drug interaction prediction, transporter-mediated interaction prediction, and pediatric PK prediction. The purpose of this review is to introduce PBPK and illustrates one of its application areas, particularly pediatric PK prediction by utilizing existing adult PK data and in vitro data. The evaluation of the initial PBPK for adult was done by comparing with experimental PK profiles and the scaling from adult to pediatric was conducted using age-related changes in size such as tissue compartments, and protein binding etc. Sotalol and lorazepam were selected in this review as model drugs for this purpose and were re-evaluated using the PBPK models by GastroPlus$^{(R)}$. The challenges and strategies of PBPK models using adult PK data as well as appropriate in vitro assay data for extrapolating pediatric PK at various ages were also discussed in this paper.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.91-91
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• 2001

Nramp2, also known as DMT1 and DCT1, is a 12-transmembrane domain protein responsible for dietary iron uptake as well as metal ions such as lead, manganese, zinc, copper, nickel, cadmium, and cobalt. High expression of DMT1 increase lead uptake, and DMT1-dependent lead transport was H -dependent and inhibited by iron ions. The molecular mechanism of lead transport in CNS is as yet unknown. although interactions between iron and lead at the level of absorption have been known for some time. The process of lead uptake into astrocytes was not known yet. Nramp2 may mediate transport of heavy metal into astrocytes. We investigated whether Nramp2 mediate transport of lead into astrocytes. And we do whether Nramp2 was expressed highly by deprivation of iron in Astrocytes, and lead uptake into astrocytes was influenced by expression of Nramp2. Immortalized human fetal astrocyte(SV-FHA) cells were cultured in medium containing Dulbecco's modified Eagle's medium and treated with Deferoxamine. Northern blot analysis was done for determining mRNA level of DMT1 and lead uptake assay was done in incubation condition of pH 5.5 and 7.4.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.475-481
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• 2016

PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine $D_3$ receptors ($D_3R$), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine $D_2$ receptor ($D_2R$) and $D_3R$ in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of $D_2R$ were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of $D_3R$ were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on $D_3R$ functions.

• Journal of Genetic Medicine
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• v.10 no.2
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• pp.88-93
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• 2013

Alexander disease (ALXD) is a rare demyelinating disease of the white matter of the brain that is caused by a mutation in the glial fibrillary acidic protein (GFAP) gene. The overexpression of GFAP in astrocytes induces a failure in the developmental growth of the myelin sheath. The neurodegenerative destruction of the myelin sheath of the white matter is accompanied by an accumulation of abnormal deposits of Rosenthal fibers in astrocytes, which is the hallmark of ALXD. The disease can be divided into four groups based on the onset age of the patients: neonatal, infantile, juvenile, or adult. Early-onset disease is more severe, progresses rapidly, and results in a shorter life span than late-onset cases. Magnetic resonance imaging and genetic tests are mostly used for diagnostic purposes. Pathological tests of brain tissue for Rosenthal fibers are definitive diagnostic methods. Therapeutic strategies are being investigated. Ceftriaxone, which is an enhancer of glial glutamate transporter (GLT-1) expression, is currently in clinical trials for the treatment of patients with ALXD. To date, there are no clinically available treatments. The cause, pathology, pathophysiology, inheritance, clinical features, diagnosis, and treatment of ALXD will be reviewed comprehensively.

• Journal of Genetic Medicine
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• v.10 no.1
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• pp.43-46
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• 2013

Adrenoleukodystrophy (ALD) is an X-linked disorder which has diverse constellation of clinical pictures, ranging from the severe childhood cerebral form to adrenocortical insufficiency without neurological manifestations. This disorder is caused by the mutations in the ABCD1 gene encoding the adrenoleukodystrophy protein (ALDP), a transporter in the peroxisome membrane. ALD in most cases is inherited from one parent. Here, we report an incidentally identified sporadic case with ALD after traffic accident. He had adrenocortical insufficiency as well as abnormal findings in brain image. Genetic testing of ABCD1 gene revealed a previously reported mutation. With the description of clinical features of ALD in this patient, we discussed the difficulty in determining an appropriate therapeutic option for ALD patients with minimal neurological manifestation.

• The Plant Pathology Journal
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• v.35 no.6
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• pp.635-643
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• 2019

To detect Xanthomonas arboricola pv. pruni, a loopmediated isothermal amplification (LAMP) detection method were developed. The LAMP assay was designed to test crude plant tissue without pre-extraction, or heating incubation, and without advanced analysis equipment. The LAMP primers were designed by targeting an ABC transporter ATP-binding protein, this primer set was tested using the genomic DNA of Xanthomonas and non-Xanthomonas strains, and a ladder product was generated from the genomic DNA of X. arboricola pv. pruni strain but not from 12 other Xanthomonas species strains and 6 strains of other genera. The LAMP conditions were checked with the healthy leaves of 31 peach varieties, and no reaction was detected using either the peach leaves or the peach DNA as a template. Furthermore, the high diagnostic accuracy of the LAMP method was confirmed with 13 X. arboricola pv. pruni strains isolated from various regions in Korea, with all samples exhibiting a positive reaction in LAMP assays. In particular, the LAMP method successfully detected the pathogen in diseased peach leaves and fruit in the field, and the LAMP conditions were proven to be a reliable diagnostic method for the specific detection and identification of X. arboricola pv. pruni in peach orchards.