• Korean Journal of Clinical Pharmacy
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• v.32 no.1
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• pp.13-19
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• 2022

Background: The use of combination therapy and fixed-dose combination therapy is increasing for the treatment of type 2 diabetes. Sodium glucose cotransporter-2 inhibitor (SGLT2i) is a drug class used in combination with metformin. Methods: Type 2 diabetes patients on SGLT2i/metformin combination therapy were extracted from the 2019 Health Insurance Review & Assessment Service-National Patients Sample. On July 1, 2019, SGLT2i and metformin fixed-dose combination (SGLT2i/metformin FDC) and two-pill combination (TPC) groups were identified, and a chi-square test and multiple logistic regression were performed. Results: Of total 2,992 patients, 1,077 (36%) were prescribed SGLT2i/metformin FDC and 1,915 (64%) were prescribed TPC. We found that the most common comorbidities were in the order of dyslipidemia, gastrointestinal disease, and hypertension. Multiple logistic regression analysis showed that the use of SGLT2i/metformin FDC was lower than TPC in patients with diabetic neuropathy (OR=0.76, p=0.008). Clinic (OR=2.09, p<0.001) and general hospital (OR=1.40, p=0.019) showed higher tendency to prescribe SGLT2i/metformin FDC compared to tertiary hospital. The tendency of prescribing SGLT2i/metformin FDC was lower in Kyeonggi (OR=0.79, p=0.037), Gyeongsang (OR=0.77, p=0.025) and Chungcheong (OR=0.68, p=0.007) than Seoul. Conclusion: Factors related to the use of SGLT2i/metformin FDC in patients with type 2 diabetes were complication, medical institution and region. The tendency to prescribe SGLT2i/metformin FDC was relatively higher in clinics than in tertiary general hospitals and in Seoul than in other regions.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.2
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• pp.232-237
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• 2009

The expression of SGLT-1 mRNA has been reported in the small intestine of mammals and the rectum of chickens. However, the expression and functional significance of SGLT-1 in bovine rectum is not known. In this study, we studied the effects of fasting and grazing on SGLT-1 gene expression in biopsy epithelial tissue of bovine rectum. In Japanese Black beef cattle, i) SGLT-1 gene expression was measured by quantitative real-time PCR in the biopsy rectal epithelia samples obtained through an endoscope, ii) SGLT-1 gene expression in the rectal epithelial tissues increased at 48 and 72 h after fasting correlating with a decrease in body weight. iii) SGLT-1 gene expression decreased after one month from the start of grazing (May to June) and then stabilized until the end of the grazing period (June to October) in the rectal epithelial tissues of grazing cattle. In conclusion, it is clear that SGLT-1 gene expression in the rectal epithelial tissue is increased by a restricted dietary condition.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.55-62
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• 2019

HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the $T_{1/2}$ was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice ($19.32{\pm}1.16mg/g$) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.

• 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.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.250-256
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• 2004

Cordyceps possesses numerous health-promoting ingredients including hypoglycemic agents. The mechanism for the reduction of circulatory sugar content, however, is still not fully understand. In this study, 4-beta acetoxyscirpendiol (ASD) was purified from the methanolic extracts from fruiting bodies of Paecilomyces tenuipes. Na+/Glucose transporter-1 (SGLT-1) was expressed in the Xenopus oocytes. The effect of ASD on the oocyte expressed SGLT-1 was analyzed utilizing the voltage clamp and 2-deoxy-D-glucose (2-DOG) uptake studies. ASD was shown to significantly inhibit SGLT-1 activity compared to the non-treated control in a dose- dependent manner. In the presense of its two derivatives (diacetoxyscirpenol or 15-acetoxyscirpendiol), SGLT-1 activity was greatly inhibited similarly as ASD. Between ASD derivatives, 15-acetoxyscirepenol showed inhibition equivalent to that of ASD while diacetoxyscirpenol did less degree of inhibition. Insummary , these results strongly indicate that ASD in P. tenuipes may serve as a functional substance in lowering blood sugar in the circulatory system. ASD and its derivatives can be utilized as inhibitors of SGLT-1.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.2938-2940
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• 2011

Novel C-aryl glucoside SGLT2 inhibitors containing triazine motif were designed and synthesized for biological evaluation. Among the compounds assayed, triazine containing methoxy moiety 18 demonstrated the best in vitro inhibitory activity against hSGLT2 in this series to date ($IC_{50}$ = 24.9 nM).

• 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.

• 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.

• 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.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.76.1-76.14
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• 2022

Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca²⁺/P⁵⁺ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.