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Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes
PURPOSE: Oral agents are needed that improve glycemic control without increasing hypoglycemic events in patients with type 1 diabetes (T1D). Sotagliflozin may meet this need, because this compound lowers blood glucose through the insulin-independent mechanisms of inhibiting kidney SGLT2 and intestin...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346285/ https://www.ncbi.nlm.nih.gov/pubmed/25759591 http://dx.doi.org/10.2147/DMSO.S76342 |
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author | Powell, David R Doree, Deon Jeter-Jones, Sabrina Ding, Zhi-Ming Zambrowicz, Brian Sands, Arthur |
author_facet | Powell, David R Doree, Deon Jeter-Jones, Sabrina Ding, Zhi-Ming Zambrowicz, Brian Sands, Arthur |
author_sort | Powell, David R |
collection | PubMed |
description | PURPOSE: Oral agents are needed that improve glycemic control without increasing hypoglycemic events in patients with type 1 diabetes (T1D). Sotagliflozin may meet this need, because this compound lowers blood glucose through the insulin-independent mechanisms of inhibiting kidney SGLT2 and intestinal SGLT1. We examined the effect of sotagliflozin on glycemic control and rate of hypoglycemia measurements in T1D mice maintained on a low daily insulin dose, and compared these results to those from mice maintained in better glycemic control with a higher daily insulin dose alone. MATERIALS AND METHODS: Nonobese diabetes-prone mice with cyclophosphamide-induced T1D were randomized to receive one of four daily treatments: 0.2 U insulin/vehicle, 0.05 U insulin/vehicle, 0.05 U insulin/2 mg/kg sotagliflozin or 0.05 U insulin/30 mg/kg sotagliflozin. Insulin was delivered subcutaneously by micro-osmotic pump; the day after pump implantation, mice received their first of 22 once-daily oral doses of sotagliflozin or vehicle. Glycemic control was monitored by measuring fed blood glucose and hemoglobin A(1c) levels. RESULTS: Blood glucose levels decreased rapidly and comparably in the 0.05 U insulin/sotagliflozin-treated groups and the 0.2 U insulin/vehicle group compared to the 0.05 U insulin/vehicle group, which had significantly higher levels than the other three groups from day 2 through day 23. A(1c) levels were also significantly higher in the 0.05 U insulin/vehicle group compared to the other three groups on day 23. Importantly, the 0.2 U insulin/vehicle group had, out of 100 blood glucose measurements, 13 that were <70 mg/dL compared to one of 290 for the other three groups combined. CONCLUSION: Sotagliflozin significantly improved glycemic control, without increasing the rate of hypoglycemia measurements, in diabetic mice maintained on a low insulin dose. This sotagliflozin-mediated improvement in glycemic control was comparable to that achieved by raising the insulin dose alone, but was not accompanied by the increased rate of hypoglycemia measurements observed with the higher insulin dose. |
format | Online Article Text |
id | pubmed-4346285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43462852015-03-10 Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes Powell, David R Doree, Deon Jeter-Jones, Sabrina Ding, Zhi-Ming Zambrowicz, Brian Sands, Arthur Diabetes Metab Syndr Obes Original Research PURPOSE: Oral agents are needed that improve glycemic control without increasing hypoglycemic events in patients with type 1 diabetes (T1D). Sotagliflozin may meet this need, because this compound lowers blood glucose through the insulin-independent mechanisms of inhibiting kidney SGLT2 and intestinal SGLT1. We examined the effect of sotagliflozin on glycemic control and rate of hypoglycemia measurements in T1D mice maintained on a low daily insulin dose, and compared these results to those from mice maintained in better glycemic control with a higher daily insulin dose alone. MATERIALS AND METHODS: Nonobese diabetes-prone mice with cyclophosphamide-induced T1D were randomized to receive one of four daily treatments: 0.2 U insulin/vehicle, 0.05 U insulin/vehicle, 0.05 U insulin/2 mg/kg sotagliflozin or 0.05 U insulin/30 mg/kg sotagliflozin. Insulin was delivered subcutaneously by micro-osmotic pump; the day after pump implantation, mice received their first of 22 once-daily oral doses of sotagliflozin or vehicle. Glycemic control was monitored by measuring fed blood glucose and hemoglobin A(1c) levels. RESULTS: Blood glucose levels decreased rapidly and comparably in the 0.05 U insulin/sotagliflozin-treated groups and the 0.2 U insulin/vehicle group compared to the 0.05 U insulin/vehicle group, which had significantly higher levels than the other three groups from day 2 through day 23. A(1c) levels were also significantly higher in the 0.05 U insulin/vehicle group compared to the other three groups on day 23. Importantly, the 0.2 U insulin/vehicle group had, out of 100 blood glucose measurements, 13 that were <70 mg/dL compared to one of 290 for the other three groups combined. CONCLUSION: Sotagliflozin significantly improved glycemic control, without increasing the rate of hypoglycemia measurements, in diabetic mice maintained on a low insulin dose. This sotagliflozin-mediated improvement in glycemic control was comparable to that achieved by raising the insulin dose alone, but was not accompanied by the increased rate of hypoglycemia measurements observed with the higher insulin dose. Dove Medical Press 2015-02-26 /pmc/articles/PMC4346285/ /pubmed/25759591 http://dx.doi.org/10.2147/DMSO.S76342 Text en © 2015 Powell et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Powell, David R Doree, Deon Jeter-Jones, Sabrina Ding, Zhi-Ming Zambrowicz, Brian Sands, Arthur Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes |
title | Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes |
title_full | Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes |
title_fullStr | Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes |
title_full_unstemmed | Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes |
title_short | Sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes |
title_sort | sotagliflozin improves glycemic control in nonobese diabetes-prone mice with type 1 diabetes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346285/ https://www.ncbi.nlm.nih.gov/pubmed/25759591 http://dx.doi.org/10.2147/DMSO.S76342 |
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