Sergliflozin etabonate, a selective SGLT2 inhibitor, improves glycemic control in streptozotocin-induced diabetic rats and Zucker fatty rats

Fujimori, Yoshikazu; Katsuno, Kenji; Ojima, Kazuma; Nakashima, Ikumi; Nakano, Shigeru; Ishikawa-Takemura, Yukiko; Kusama, Hiroshi; Isaji, Masayuki

doi:10.1016/j.ejphar.2009.03.007

Cited by 65 publications

(58 citation statements)

References 22 publications

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“…Furthermore, the HbA1c levels in GK rats were also dose-dependently reduced after 38 d of treatment, suggesting that the hyperglycemia in these type 2 diabetic animal models can be treated by chronic administration of the SGLT2 inhibitor SHR3824. Although SGLT2 inhibitors have been demonstrated to decrease body weight in clinical studies, the chronic administration of SHR3824 affected neither the body weight nor the food intake in GK rats or db/db mice, as reported previously by several other SGLT2 inhibitor studies [13,29] .…”

Section: Discussionmentioning

confidence: 71%

SHR3824, a novel selective inhibitor of renal sodium glucose cotransporter 2, exhibits antidiabetic efficacy in rodent models

et al. 2014

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Aim: The sodium glucose cotransporter 2 (SGLT2) plays an important role in renal glucose reabsorption, thus serves as a new target for the treatment of diabetes. The purpose of this study was to evaluate SHR3824 as a novel selective SGLT2 inhibitor and to characterize its in vivo effects on glucose homeostasis. The effects of chronic administration of SHR3824 on peripheral insulin sensitivity and pancreatic β-cell function were also investigated. Methods: The in vitro potency and selectivity of SHR3824 were assessed in HEK293 cells transfected with human SGLT2 or SGLT1. Acute and multi-dose studies were performed on ICR mice, GK rats and db/db mice to assess the ability of SHR3824 to enhance urinary glucose excretion and improve blood glucose levels. 2-Deoxyglucose uptake and insulin immunohistochemical staining were performed in the soleus muscle and pancreas, respectively, of db/db mice. A selective SGLT2 inhibitor BMS512148 (dapagliflozin) was taken as positive control. Results: SHR3824 potently inhibited human SGLT2 in vitro, but exerted much weak inhibition on human SGLT1 (the IC 50 values of SHR3824 against human SGLT2 and SGLT1 were 2.38 and 4324 nmol/L, respectively). Acute oral administration of SHR3824 (0.3, 1.0, 3.0 mg/kg) dose-dependently improved glucose tolerance in ICR mice, and reduced hyperglycemia by increasing urinary glucose excretion in GK rats and db/db mice. Chronic oral administration of SHR3824 (0.3, 1.0, 3.0 mg·kg -1 ·d -1 ) dose-dependently reduced blood glucose and HbA1c levels in GK rats and db/db mice, and significantly increased insulin-stimulated glucose uptake in the soleus muscles and enhanced insulin staining in the islet cells of db/db mice. Conclusion: SHR3824 is a potent and selective SGLT2 inhibitor and exhibits antidiabetic efficacy in several rodent models, suggesting its potential as a new therapeutic agent for the treatment of type 2 diabetes.

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Section: Discussionmentioning

confidence: 71%

SHR3824, a novel selective inhibitor of renal sodium glucose cotransporter 2, exhibits antidiabetic efficacy in rodent models

et al. 2014

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“…(n=4-5). *Pb0.05, **Pb0.01 vs. vehicle group [20]. Its selectivity towards human SGLT2 was higher as compared to human SGLT1.…”

Section: Remigliflozinmentioning

confidence: 89%

“…Sergliflozin etabonate (Active form of Sergliflozin) encouraged excretion of glucose depending on blood glucose level. Upon chronic administration of sergliflozinetabonate to Zuker fatty rats there is no alteration in body weight (622.6 ± 12.4, 614.7 ± 23.2, and 615.8 ± 15.6g for vehicle, 10mg/kg and 30 mg/kg group respectively) as well as the food intake (30.6 ± 2.0, 29.5 ± 2.5, and 32.1 ± 1.3g for vehicle 10mg/ kg and 30 mg/kg group respectively) but it reduces both the glycated heamoglobin ( Figures 3A,3B) and fasting plasma glucose (Figure 4) [20].…”

Section: Sergiflozin Etabonatementioning

confidence: 99%

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

et al. 2014

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“…The features of nSTZ rats as a T2D model make this model valuable for evaluation of many hypoglycemic drugs, including a sulfonylurea [31], a thiazolidinedione (pioglitazone) [32], a biguanide (metformin) [33], a glucose sensor enhancer [34], a DPPIV-i [35], and an SGLT2 inhibitor [36]. nSTZ rats are also a useful model for assessment of therapeutic drugs that enhance -cell regeneration.…”

Section: Drug Treatmentmentioning

confidence: 99%

Non-Obese Type 2 Diabetes Animals Models

Ishii¹,

Ohta²,

Sasase³

2012

Glucose Tolerance

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Sergliflozin etabonate, a selective SGLT2 inhibitor, improves glycemic control in streptozotocin-induced diabetic rats and Zucker fatty rats

Cited by 65 publications

References 22 publications

SHR3824, a novel selective inhibitor of renal sodium glucose cotransporter 2, exhibits antidiabetic efficacy in rodent models

SHR3824, a novel selective inhibitor of renal sodium glucose cotransporter 2, exhibits antidiabetic efficacy in rodent models

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

Non-Obese Type 2 Diabetes Animals Models

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