• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.183-188
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• 2001

To elucidate antidiabetic effect and mechanism(s) of acarbose in a polygenic spontaneous hyperglycemic and hyperinsulinemic diabetic animal model, $KKA^y$ mice, acarbose was administered orally for 4 weeks and effects on body weight, plasma glucose and insulin levels, genetic expressions of intestinal sucrase-isomaltase (SI), sodium-glucose cotransporter (sGLT1) and glucose transporter in quadriceps muscle (GLUT4) were examined in this study. Although no differences in body weight were detected between control and acarbose-treated groups, plasma glucose level in acarbose-treated group was markedly reduced as compared to the control. In the mechanism study, acarbose downregulated the SI and SGLT1 gene expressions, and upregulated the GLUT4 mRNA and protein expressions when compared to the control group. In conclusion, the data obtained strongly implicate that acarbose can prevent the hyperglycemia in $KKA^y$ mice possibly through blocking intestinal glucose absorption by downregulations of SI and sGLT1 mRNA expressions, and upregulation of skeletal muscle GLUT4 mRNA and protein expressions.

• Korean journal of food and cookery science
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• v.18 no.1
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• pp.94-100
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• 2002

The dietary carbohydrates are mainly digested and adsorbed at small intestine. We developed a new food additive as an egg yolk antibody(1gY) against maltase, sucrase and sodium dependent g1ucose cotransporter(SGLT) for the regulation of blood glucose level and weight control. The maltase, sucrase and SGLT were purified from porcine small intestine which is very similar to that of human in physiological characteristics. The purification step contained an ultracentrifugation, ion exchange chromatography and hydrophobic chromatography. The hens were immunized by purified protein and the IgY activities against immunized antigens were determined. This antibody obtained from the immunized hen's egg yolks directly inhibited the activities of maltase and sucrase in vitro. And the IgY delayed and decreased the increment of blood g1ucose level after administration of maltose, sucrose and glucose in rat about 30 to 60%. The results of this study suggest that the IgY inhibiting the carbohydrate digestion could be used as functional food materials for weight control and regulation of blood glucose level in diabetes.

• International Journal of Heart Failure
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• v.6 no.2
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• pp.47-55
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• 2024

Heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) represent over half of heart failure cases but lack proven effective therapies beyond sodium-glucose cotransporter 2 inhibitor and diuretics. HFmrEF and HFpEF are heterogeneous conditions requiring precision phenotyping to enable tailored therapies. This review covers concepts on precision medicine approaches for HFmrEF and HFpEF. Areas discussed include HFmrEF mechanisms, anti-inflammatory and antifibrotic treatments for obesity-related HFpEF, If inhibition for HFpEF with atrial fibrillation, and mineralocorticoid receptor antagonism for chronic kidney disease-HFpEF. Incorporating precision phenotyping and matched interventions in HFmrEF and HFpEF trials will further advance therapy compared to blanket approaches.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.257-267
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• 1996

Diabetes mellitus is associated with a wide range of pathophysiologic changes in the kidney. This study was designed to examine the mechanisms by which glucose modulates the expression of polarized membrane transport functions in primary cultured rabbit renal proximal tubule cells. Results are as follows: The rate of 30 minute $Rb^{+}$ uptake was significantly higher($137.76{\pm}5.40%$) in primary renal tubular cell cultures treated with 20 mM glucose than that of 5 mM glucose. Not the level of mRNA for the ${\alpha}$ subunit of Na, K-ATPase but that of ${\beta}$ subunit was elevated in primary cultures treated with high glucose. The initial rate of methyl-${\alpha}$-D-glucopyranoside(${\alpha}$-MG) uptake was significantly lower($71.91{\pm}3.02%$) in monolayers treated with 20 mM glucose than that of 5 mM glucose. There was a tendency of an increase in phlorizin binding site in cells treated with 5 mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. TPA inhibited $Rb^{+}$ uptake by $63.61{\pm}1.94\;and\;45.80{\pm}1.36%$ and ${\alpha}$-MG uptake by $48.54{\pm}3.69\;and\;41.87{\pm}6.70%$ in the cells treated with 5 and 20 mM glucose, respectively. Also TPA inhibited mRNA expression of Na/glucose cotransporter in cells grown in 5mM glucose medium. cAMP significantly stimulated ${\alpha}$-MG uptake by $114.65{\pm}5.70%$ in cells treated with 5mM glucose, while it did not affect ${\alpha}$-MG uptake in cell treated with 20 mM glucose. However, cAMP inhibited $Rb^{+}$ uptake by $76.69{\pm}4.16\;and\;66.87{\pm}2.41%$ in cells treated with 5 and 20 mM glucose, respectively. In conclusion, the activity of the renal proximal tubular Na,K-ATPase is elevated in high glucose concentration. In contrast, the activity of the Na/glucose cotransport system is inhibited. High glucose may in part affect the activity of the Na,K-ATPase and the Na/glucose cotransport system by controlling the protein kinase C and/or A signal transduction pathway in primary cultured renal proximal tubule cells.

• Korean Journal of Ichthyology
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• v.32 no.3
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• pp.117-129
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• 2020

The body color pattern in fish is a distinctive feature for species identification. The blass bloched rockfish Sebastes pachycephalus is a commercially important marine fish species, distributed in the central and southern parts of Korea and south Hokkaido of Japan. It has a morphological feature divided into four subspecies according to with or lacking distinct spots on the body surface, and to the location of markings on the body surface. However, the genetic basis of body color pattern of S. pachycephalus is still unknown. Thus we analyzed the transcriptome of S. pachycephalus skin samples using RNA-seq analysis to investigate functional genes related to body color patterns. The experimental skin samples were prepared by classified into 'Wild type' (lacking distinct spots and markings) and 'Color type' (with distinct spots and marking). Two skin sample transcriptomes were compared pairwise and the results revealed that were 164 differentially expressed unigenes in the skin samples of 'Wild type' and 'Color type'. Gene Ontology analysis of 164 differentially expressed unigenes showed that these genes were included in the functional group of molecular function (2 genes), biological process (46 genes), and cellular component (6 genes). There were several genes that body color type skin specific expression and the genes were CTL (Galactose-specific lectin nattectin), CUL1 (Cullin-1), CMAS (N-acylneuraminate cytidylyltransferase), NMRK2 (Nicotinamide riboside kinase 2), ALOXE3 (Hydroperoxide isomerase ALOXE3), SLC4A7 (sodium bicarbonate cotransporter 3). Our study is the first attempt to search for functional genes involved in the formation of body color patterns in S. pachycephalus. The differentially expressed unigenes obtained in this study can be used as candidate genes for functional gene study related to body coloration of fish.

• Journal of fish pathology
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• v.24 no.1
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• pp.11-18
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• 2011

This study was aimed to investigate the pathophysiological changes of olive flounder, Paralichthys olivaceus suffering from emaciation. A plasma osmolality was higher in the emaciated and control flounders than that of normal teleost, suggesting osmoregulatory failure in both of them. Also, the control in the same stock with emaciated flounder seem to be classified into a primary degree of emaciation. According to microscopic observations, the inflammatory responses were observed in the submucosal layer of anterior intestine, although the some of mucosal intestinal epithelium still remained. It was suggested that the pathological changes of the anterior part give rise to malabsorption of nutrients through the mucosa. In the posterior intestine and rectum, the mucosal epithelium were almostly sloughed off and severe inflammatory responses were observed in the submucosa. Immunoreaction for NKCC was not detected in the mucosal epithelial cells in intestine because of sloughing of epithelium. These changes would lead to functional disorder in the intestine, such as malabsorption of nutrients and osmoregulatory failure. Also important is to investigate the recovery phase.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.413-417
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• 2002

Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria that has recently been reported to be linked to thiazide- sensitive Na-Cl cotransporter gene mutation. In this study, we performed renal clearance studies to differentiate Gitelman's from Bartter's syndrome and to confirm the diagnosis in two patients clinically diagnosed with Gitelman's syndrome. Each patient was hydrated by 20 mL/kg body weight of oral water within 30 minutes, which was followed by intravenous half saline. When urinary flow reached 10 mL/min, samples of urine and serum were obtained to calculate the osmolar clearance, free water clearance, chloride clearance, and distal fractional chloride reabsorption. Subsequently, furosemide or hydrochlorothiazide was administered. Samples were collected and the same parameters were calculated. In our patients, chloride clearance was increased more than 10 times after furosemide administration(2.1 : 25.7 and 2.2 : 27.4 mL/min/100 mL GFR), but not increased after hydrochlorothiazide treatment(2.1 : 1.6 and 2.2 : 2.6 mL/min/100 mL GFR). And the distal fractional chloride reabsorption was significantly decreased by furosemide injection (73% : 15% and 75% : 4.6%), whereas hydrochlorothiazide had no effect on it(73% : 63% and 75% : 78%). These findings indicate that our patients have a defect in thiazide-sensitive Na-Cl cotransporter in the distal tubule, which is compatible with the pathophysiology of Gitelman's syndrome.

• Korean Circulation Journal
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• v.54 no.5
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• pp.256-267
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• 2024

Background and Objectives: Accumulating evidence shows that sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce adverse cardiovascular outcomes. However, whether SGLT2i, compared with other antidiabetic drugs, reduce the new development of atrial fibrillation (AF) is unclear. In this study, we compared SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4is) in terms of reduction in the risk of AF in individuals with type 2 diabetes. Methods: We included 42,786 propensity score-matched pairs of SGLT2i and DPP-4i users without previous AF diagnosis using the Korean National Health Insurance Service database between May 1, 2016, and December 31, 2018. Results: During a median follow-up of 1.3 years, SGLT2i users had a lower incidence of AF than DPP-4i users (1.95 vs. 2.65 per 1,000 person-years; hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97; p=0.028]). In individuals without heart failure, SGLT2i users was associated with a decreased risk of AF incidence (HR, 0.70; 95% CI, 0.52-0.94; p=0.019) compared to DPP-4i users. However, individuals with heart failure, SGLT2i users was not significantly associated with a change in risk (HR, 1.04; 95% CI, 0.44-2.44; p=0.936). Conclusions: In this nationwide cohort study of individuals with type 2 diabetes, treatment with SGLT2i was associated with a lower risk of AF compared with treatment with DPP-4i.

• Journal of Cardiovascular Imaging
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• v.30 no.3
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• pp.153-168
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• 2022

Recent studies have shown that sodium/glucose cotransporter 2 (SGLT2) inhibitors might exert favourable changes on cardiac parameters as observed on cardiovascular imaging. We conducted a systematic review and meta-analysis to determine the effects of SGLT2 inhibitors on cardiac imaging parameters. Four electronic databases (PubMed, Embase, Cochrane, Scopus) were searched for studies in which the effects of SGLT2 inhibitors on cardiac imaging parameters were examined. Studies in which a population was administered SGLT2 inhibitors and analysed by echocardiography and/or cardiac magnetic resonance (CMR) imaging were included. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. A total of 11 randomized controlled trials was included with a combined cohort of 910 patients. Comparing patients receiving SGLT2 inhibitors with subjects receiving placebo, the mean change in CMR-measured left ventricular mass (LVM) was -3.87 g (95% confidence interval [CI], -7.77 to 0.04), that in left ventricular end-systolic volume (LVESV) was -5.96 mL (95% CI, -10.52 to -1.41) for combined LVESV outcomes, that in left atrial volume index (LAVi) was -1.78 mL/m² (95% CI, -3.01 to -0.55) for combined LAVi outcomes, and that in echocardiography-measured E/e' was -0.73 (95% CI, -1.43 to -0.03). Between-group differences were not observed in LVM and LVESV after indexation. The only between-group difference that persisted was for LAVi. Treatment with SGLT2 inhibitors resulted in reduction in LAVi and E/e' on imaging, indicating they might have an effect on outcomes associated with LV diastolic function.

• BMB Reports
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• v.38 no.2
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• pp.211-217
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• 2005

Cordyceps, an entomopathogenic fungus, contains many health-promoting ingredients. Recent reports indicate that the consumption of cordyceps helps reduce blood-sugar content in diabetics. However, the mechanism underlying this reduction in circulatory sugar content is not fully understood. Methanolic extracts were prepared from the fruiting bodies of Paecilomyces tenuipes, and 4-beta acetoxyscirpendiol (4-ASD) was eventually isolated and purified. $Na^+$/Glucose transporter-1 (SGLT-1) was expressed in Xenopus oocytes, and the effect of 4-ASD on SGLT-1 was analyzed utilizing a voltage clamp and by performing 2-deoxy-D-glucose (2-DOG) uptake studies. 4-ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose-dependent manner. In the presence of the derivatives of 4-ASD (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited in an 4-ASD-like manner. Of these derivatives, 15-acetoxyscirepenol inhibited SGLT-1 as well as 4-ASD, whereas diacetoxyscirpenol was slightly less effective. Taken together, these results strongly indicate that 4-ASD in P. tenuipes may lower blood sugar levels in the circulatory system. We conclude that 4-ASD and its derivatives are effective SGLT-1 inhibitors.