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Cited by 240

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Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models

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Liang, Yin, Arakawa, Kenji, Ueta, Kiichiro, Matsushita, Yasuaki, Kuriyama, Chiaki, Martin, Tonya, Du, Fuyong, Liu, Yi, Xu, June, Conway, Bruce, Conway, Jamie, Polidori, David, Ways, Kirk, Demarest, Keith·2012·PLoS ONE
DOI 10.1371/journal.pone.0030555
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Abstract

BACKGROUND: Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). METHODS: (14)C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; (3)H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RT(G)) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. RESULTS: Treatment with canagliflozin 1 mg/kg lowered RT(G) from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RT(G). Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio. CONCLUSIONS: Canagliflozin lowered RT(G) and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity.

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Metadata

Authors
Liang, Y., Arakawa, K., Ueta, K., Matsushita, Y., Kuriyama, C., Martin, T., Du, F., Liu, Y., Xu, J., Conway, B., Conway, J., Polidori, D., Ways, K., & Demarest, K.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-02-15
Volume
7
Issue
2
Pages
e30555
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0030555
OpenAlex
W2021988691
Cited by
240
References
3
FWCI
19.10
Type
journal article
Language
en
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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CoChat. (2026). Citation check: Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models. https://app.cochat.ai/papers/10.1371/journal.pone.0030555
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Liang, Y., Arakawa, K., Ueta, K., Matsushita, Y., Kuriyama, C., Martin, T., Du, F., Liu, Y., Xu, J., Conway, B., Conway, J., Polidori, D., Ways, K., & Demarest, K. (2012). Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models. PLoS ONE. https://doi.org/10.1371/journal.pone.0030555

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