• 고신대학교 의과대학 학술지
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• 제33권3호
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• pp.402-408
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• 2018

Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. In this study, we presented the case of a 59-year-old male who developed hyperosmolar hyperglycemic state (HHS), possibly caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents. This case highlights that HHS can develop in patients with diabetes treated with SGLT2 inhibitors.

• Fisheries and Aquatic Sciences
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• 제18권2호
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• pp.173-181
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• 2015

We identified the $Na^+-K^+-2Cl^-$ cotransporter 2 (NKCC2) cDNA isoform from starry flounder, Platichthys stellate. The NKCC2 cDNA encoded a polypeptide of 1,043 amino acids representing 12 putative transmembrane domains based on the bioinformatic topology prediction. In addition, starry flounder NKCC2 possessed highly conserved residues within transmembrane domain 4, known as an essential site for its function. End-point reverse transcription-polymerase chain reaction analysis revealed that the NKCC2 transcript was moderately expressed only in the anterior and posterior intestines and the rectum. The NKCC2 mRNA level in the rectum, but not in other segments, was significantly induced 3 days post Streptococcus parauberis challenge, indicating that excess salt may be transported into the rectum. Taken together, our data indicate that an S. parauberis infection could tip the intestinal fluid balance in favor of fluid accumulation, indicating that bacterial pathogens can interfere with intestinal osmotic balance and normal mucosal immune homeostasis.

• International Journal of Oral Biology
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• 제33권4호
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• pp.143-147
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• 2008

The sodium bicarbonate cotransporter (NBC) protein is functionally expressed in salivary glands. In this experiment, we examined the role of NBC in $HCO_3^-$ formation in human parotid gland acinar cells. Intracellular pH (pHi) was measured in 2'-7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-loaded cells. Acetazolamide (0.1 mM) and 4,4'-diisothio cyanatostilbene-2,2'-disulphonic acid (DIDS, 0.5 mM) were used as specific inhibitors of carbonic anhydrase and NBC, respectively. The degree of inhibition was assessed by measuring the pHi recovery rate (${\Delta}pHi$/min) after cell acidification using an ammonium prepulse technique. In control experiments, ${\Delta}pHi$/min was $1.40{\pm}0.06$. Treatment of cells with 0.5 mM DIDS or 0.1 mM acetazolamide significantly reduced ${\Delta}pHi$/min to $1.14{\pm}0.14$ and $0.74{\pm}0.15$, respectively. Simultaneous application of DIDS and acetazolamide further reduced ${\Delta}pHi$/min to $0.47{\pm}0.10$. Therefore, DIDS and acetazolamide reduced ${\Delta}pHi$/min by 19% and 47%, respectively, while simultaneous application of both DIDS and acetazolamide caused a reduction in ${\Delta}pHi$/min of 67%. These results suggest that in addition to carbonic anhydrase, NBC also partially contributes to $HCO_3^-$ formation in human parotid gland acinar cells.

• Archives of Pharmacal Research
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• 제18권1호
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• pp.12-17
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• 1995

It is essential to clone the preptide transporter in order to obtain better understanding of its molecular structure, regulation, and substrate specificity. Characteristics of an endogenous peptide transporter in oocytes were studied along with expression of an exogenous protor/peptide cotransporter from rabbit intestine. And further efforts toward cloning the transporter were performed. The presence of an endogenous peptide transporter was detected in Xenopus laevis oocytes by measuring the uptake of $0.25/{mu}M(10{\;}{\mu}Ci/ml)[^3H]$-glycylsarcosine (Gly-Sar) at pH 5.5 with or without inhibitors. Yptake of Gly-Sae in oocytes was significantly inhibited by $25{\mu}M$ glycine nd sarcosine. This result suggests that a selective transporter is involved in the endogneous uptake of dipeptides. Collagenase treatment of oocytes used to strip oocytes from ovarian follicles did not affect the Gly-Sar uptake. Changing pH from 5.5 to 7.5 did not affect the Gly-Sae uptake significantly, suggesting no depedence of the endogenous transporter on a transmembrane proton gradient. An exogenous $H^+/pep-tide$ contransported was expressed after microinjection of polyadenylated messenger ribonucleic acid $[poly(A)^+ -mRNA]$ obtained from rabbit small intestine. The Gly-Sar uptake in mRNA-injected oocytes was 9 times thigher than that in water-injected oocyltes. Thus, frog occytes can be utilized fro expression cloning of the genes encoding intestinal $H^+$peptide contransporters. Size fractionation of mRNA was successfully obtained using this technique.

• Journal of Korean Dental Science
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• 제4권2호
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• pp.73-78
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• 2011

Purpose: $HCO_3{^-}$ is the most important ion to buffer the acidity of saliva. The transport of $HCO_3{^-}$ is mediated by electrogenic $Na^+/HCO_3{^-}$ cotransporter 1 (NBCe1), which expressed in various tissues including salivary glands, kidney and pancreas, etc. This experiment was performed to investigate regulatory site of NBCe1involved in the pH regulation using various mutants of NBCe1. Materials and Methods: Human parotid gland NBCe1 (hpNBCe1) and mutants by deletion of 1~285 bp and 1~1,035 bp were prepared. After microinjection of each cRNA to oocytes of Xenopus laevis, they were incubated for 2~3 days. The function of each protein was tested by electrophysiological method. Results: When oocytes were exposed to the $HCO_3{^-}$ buffered solution, 1~285 bp deleted mutant hpNBCe1 evoked a marked hyperpolarization ranging from -90 mV to -160 mV (average: -134 mV; n=12) compared to the full length of hpNBCe1. Although 1~1,035 bp deleted mutant hpNBCe1 was also expressed in the plasma membrane, but it did not show any changes of membrane potentials. Conclusion: Our deletion mutant study demonstrated that 1~285 bp of the NBCe1 is the major domain to determine $HCO_3{^-}$ transport ratio.

• 당뇨병
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• 제19권3호
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• pp.135-139
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• 2018

The sodium-glucose cotransporter-2 inhibitor (SGLT2i) is a new anti-hyperglycemic agent that have function to concomitantly inhibit the reabsorption of glucose and sodium in the renal proximal convoluting tubule. Recent two cardiovascular outcome trials showed that a lower risk of cardiovascular events with SGLT2i in people with type 2 diabetes. In addition, prior real-world data demonstrated similar SGLT2i effects, but these studies were limited to the United States and Europe. Thus, the CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors) 2 Study was investigated cardiovascular outcomes in those initiated on SGLT2i versus other glucose-lowering drugs (oGLDs) across 6 countries in the Asia Pacific, the Middle East, and North American regions. In Korea, 336,644 episodes of initiation in SGLT2i or oGLD group between September 2014 and December 2016 were identified in Korea National Health Insurance database after propensity score matching. SGLT2i users was associated with a lower risk of all-cause death (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.67~0.77), hospitalization for heart failure (HHF) (HR, 0.87; 95% CI, 0.82~0.92), all-cause death or HHF (HR, 0.81; 95% CI, 0.78~0.85), myocardial infarction (HR, 0.81; 95% CI, 0.74~0.89), and stroke (HR, 0.82; 95% CI, 0.78~0.86) compared with oGLD users. In conclusion, initiation of SGLT2i had a lower risk of cardiovascular events in people with type 2 diabetes compared with oGLDs.

• The Korean Journal of Physiology
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• 제29권1호
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• pp.69-80
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• 1995

Renal proximal tubular hypertrophy and hyperfunction are known to be early manifestations of experimental and human diabetes. As the hypertrophy and hyperfunction have been suggested to be central components in the progression to renal failure, an understanding of their underlying causes is potentially important for the development of therapy. A primary rabbit kidney proximal tubule cell culture system was utilized to evaluate the possibility that the renal proximal tubular hypertrophy and hyperfunction observed in vivo in diabetes mellitus, can be attributed to effects of elevated glucose levels on membrane transport systems. Primary cultures of rabbit proximal tubules, which achieved confluence at 10 days, exhibited brush-border characteristics typical of proximal tubular cells. Northern analysis indicated $2.2{\sim}2.3$ and 2.0 kb Na/glucose cotransporter RNA species appeared in fresh and cultured proximal tubule cells after confluence, repectively. The cultured cells showed reduced Na/glucose cotransporter activity compared to fresh proximal tubules. Primary cultured proximal tubule cells incubated in medium containing 20 mM glucose have reduced ${\alpha}-MG$ transport compared to cells grown in 5 mM glucose. In the proximal tubule cultures incubated in medium containing 5 mM or 20 mM glucose, phlorizin at 0.5 mM inhibited 0.5 mM ${\alpha}-MG$ uptake by 84.35% or 91.85%, respectively. The uptake of 0.5 mM ${\alpha}-MG$ was similarly inhibited by 0.1 mM ouabain (41.97% or 48.03% inhibition was observed, respectively). In addition, ${\alpha}-MG$ uptake was inhibited to a greater extent when $Na^{+}$ was omitted from the uptake buffer (81.86% or 86.73% inhibition was observed, respectively). In cell homogenates derived from the primary cells grown in 5 mM glucose medium, the specific activity of the Na/K-ATPase $(6.17{\pm}1.27\;{\mu}mole\;Pi/mg\;protein/hr)$ was 1.56 fold lower than the values in cell homogenates treated with 360 mg/dl D-glucose, 20 mM $(9.67{\pm}1.22\;{\mu}mole\;Pi/mg\;protein/hr)$. Total $Rb^{+}$ uptake occurred at a significantly higher rate (1.60 fold increase) in primary cultured rabbit kidney proximal tubule cell monolayers incubated in 20 mM glucose medium $(10.48{\pm}2.45\;nM/mg\;protein/min)$ as compared with parallel cultures in 5 mM glucose medium. $Rb^{+}$ uptake rate in 5 mM glucose medium was reduced by 28% when the cultures were incubated with 1 mM ouabain. The increase of the $Rb^{+}$ uptake by rabbit kidney proximal tubule cells in 20 mM glucose could be attributed primarily to an increase in the rate of ouabain-sensitive $Rb^{+}$ uptake $(5\;mM\;to\;20\;mM;\;4.68{\pm}0.85\;to\;8.38{\pm}1.37\;nM/mg\;protein/min)$. In conclusion, the activity of the renal proximal tubular Na,K-ATPase is elevated in high glucose concentration. In contrast, the activity of the Nafglucose cotransport system is inhibited.

• Archives of Pharmacal Research
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• 제23권6호
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• pp.613-619
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• 2000

We investigated the expression profiles of rat fibrotic liver induced by bile duct ligation and scission (BDL/S) using the 3'-directed cDNA libraries. The possibility that the 3'-directed cDNA library represents the mRNA population faithfully was examined by northern blots. During the northern analysis based on fibrotic liver expression profile, we found for the first time that purine specific sodium nucleoside cotransporter (SPNT) was upregulated in BDL/S-induced fibrotic liver. To determine whether the accumulation of bile juice could affect the expression of SPNT mRNA or not, we examined the change of SPNT mRNA expression at 3, 14, 28 days after BDL/S operation. No change in SPNT expression was observed in rat liver at 3 days after surgery. In contrast, there were significant increases in SPNT expression at 14 and 28 days after surgery. We also examined whether chronic liver damage affected SPNT mRNA expression. SPNT mRNA level was significantly increased in BDL/S-induced fibrotic rat liver, whereas no significant change was obserbed in fibrotic livers chronically exposed to carbon tetrachloride or dimethylnitrosamine. From the above results, although further study might be needed, it was considered that the increment of SPNT mRNA in BDL/S liver morphological compatibility to human was remarkable.

• 셀메드
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• 제3권2호
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• pp.16.1-16.5
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• 2013

Hypertension induces many of the social costs related by cardiovascular diseases. Sodium is known as a crucial factor in inducing type I hypertension. In traditional Korean medicine, bamboo salt (BS) has been used in the attenuation of salts toxic coldness and nowadays it has shown various therapeutic effects. It contains mostly sodium chloride (about 91.7% of BS); however, the effect of BS on hypertension is still not completely understood. Thus, we investigated the effect of BS on blood pressure for the first time. Two group of BS, sun-dried salt (SDS), NaCl, or distilled water (DW, vehicle control) was administrated orally for 8 weeks. Although BS had no effect on body weight and food intake, it increased water intake (p < 0.05). The BS groups, in terms of blood pressure, was similar to the DW group; whereas the SDS and NaCl groups showed significantly increased blood pressure levels (p < 0.05). BS also decreased sodium-chloride cotransporter (NCC) mRNA expression, unlike SDS or NaCl. These observations indicate that BS may be a promising strategy for the prevention of various diseases including salt-related diseases.

• Journal of Pharmaceutical Investigation
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• 제23권3호spc1호
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• pp.31-40
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• 1993

It is essential to clone the peptide transporter in order to obtain better understanding of its molecular structure, regulation, and substrate specificity. Characteristics of an endogenous peptide transporter in oocytes were studied along with expression of an exogenous proton/peptide cotransporter from rabbit intestine. And further efforts toward cloning the transporter were performed. The presence of an endogenous peptide transporter was detected in Xenopus laevis oocytes by measuring the uptake of $0.25\;{\mu}M\;(10\;{\mu}Ci/ml)\;[^3H]-glycylsarcosine$ (Gly-Sar) at pH 5.5 with or without inhibitors. Uptake of Gly-Sar in oocytes was significantly inhibited by 25 mM Ala-Ala, Gly-Gly, and Gly-Sar (p<0.05), but not by 2.5 mM of Glu-Glu, Ala-Ala, Gly-Gly, Gly-Sar and 25 mM glycine and sarcosine. This result suggests that a selective transporter is involved in the endogenous uptake of dipeptides. Collagenase treatment of oocytes used to strip oocytes from ovarian follicles did not affect the Gly-Sar uptake. Changing pH from 5.5 to 7.5 did not affect the Gly-Sar uptake significantly, suggesting no dependence of the endogenous transporter on a transmembrane proton gradient. An exogenous $H^+/peptide$ cotransporter was expressed after microinjection of polyadenylated messenger ribonucleic acid $[poly\;(A)^+-mRNA]$ obtained from rabbit small intestine. The Gly-Sar uptake in mRNA-injected oocytes was 9 times higher than that in water-injected oocytes. Thus, frog oocytes can be utilized for expression cloning of the genes encoding intestinal $H^+/peptide$ cotransporters. Using the technique size fractionation of mRNA was sucessfully obtained.