Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice
While the autoimmune character of T1D (type 1 diabetes) is being challenged, it is currently recognized that inflammation plays a key role in its development. We hypothesized that glucotoxicity could contribute to β-cell mass destruction through participation in islet inflammation. We evaluated the...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/2813489 |
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| author | Caroline Daems Sophie Welsch Hasnae Boughaleb Juliette Vanderroost Annie Robert Etienne Sokal Philippe A. Lysy |
| author_facet | Caroline Daems Sophie Welsch Hasnae Boughaleb Juliette Vanderroost Annie Robert Etienne Sokal Philippe A. Lysy |
| author_sort | Caroline Daems |
| collection | DOAJ |
| description | While the autoimmune character of T1D (type 1 diabetes) is being challenged, it is currently recognized that inflammation plays a key role in its development. We hypothesized that glucotoxicity could contribute to β-cell mass destruction through participation in islet inflammation. We evaluated the potential of empagliflozin (EMPA) and GABA (gamma-aminobutyric acid) to protect β-cell mass against glucotoxicity and to increase β-cell mass after diagnosis of T1D. Empagliflozin is a SGLT2 (sodium-dependent glucose cotransporter) inhibitor which thereby blocks glucose recapture by the kidney and promotes glucose excretion in urine. GABA is an inhibitory neurotransmitter, which stimulates α-to-β cell transdifferentiation. In streptozotocin-treated mice, empagliflozin and/or GABA were delivered for a period of five days or three weeks. As compared to untreated T1D mice, EMPA-treated T1D mice had decreased FFA (free fatty acid) levels and improved glucose homeostasis. EMPA-treated T1D mice had higher islet density, with preserved architecture, compared to T1D mice, and EMPA-treated T1D mice also differed from T1D mice by the total absence of immune cell infiltration within islets. Islets from EMPA-treated mice were also less subjected to ER (endoplasmic reticulum) stress and inflammation, as shown by qPCR analysis. Glucose homeostasis parameters and islet area/pancreas area ratio improved, as compared to diabetic controls, when T1D mice were treated for three weeks with GABA and EMPA. T1D EMPA+GABA mice had higher glucagon levels than T1D mice, without modifications of glucagon area/islet area ratios. In conclusion, empagliflozin and GABA, used in monotherapy in streptozotocin-induced diabetic mice, have positive effects on β-cell mass preservation or proliferation through an indirect effect on islet cell inflammation and ER stress. Further research is mandatory to evaluate whether empagliflozin and GABA may be a potential therapeutic target for the protection of β-cell mass after new-onset T1D. |
| format | Article |
| id | doaj-art-88d29d91a50641d3bcc3b454f6fed84c |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-88d29d91a50641d3bcc3b454f6fed84c2025-02-03T06:00:37ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/28134892813489Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated MiceCaroline Daems0Sophie Welsch1Hasnae Boughaleb2Juliette Vanderroost3Annie Robert4Etienne Sokal5Philippe A. Lysy6Pôle PEDI, Institut de Recherche Expérimentale et Clinique, UCLouvain, Av. Hippocrate 10, B-1200 Brussels, BelgiumPôle PEDI, Institut de Recherche Expérimentale et Clinique, UCLouvain, Av. Hippocrate 10, B-1200 Brussels, BelgiumPôle PEDI, Institut de Recherche Expérimentale et Clinique, UCLouvain, Av. Hippocrate 10, B-1200 Brussels, BelgiumPôle PEDI, Institut de Recherche Expérimentale et Clinique, UCLouvain, Av. Hippocrate 10, B-1200 Brussels, BelgiumPôle d’Epidémiologie et Biostatistique, Institut de Recherche Expérimentale et Clinique, UCLouvain, Av. Hippocrate 10, B-1200 Brussels, BelgiumPôle PEDI, Institut de Recherche Expérimentale et Clinique, UCLouvain, Av. Hippocrate 10, B-1200 Brussels, BelgiumPôle PEDI, Institut de Recherche Expérimentale et Clinique, UCLouvain, Av. Hippocrate 10, B-1200 Brussels, BelgiumWhile the autoimmune character of T1D (type 1 diabetes) is being challenged, it is currently recognized that inflammation plays a key role in its development. We hypothesized that glucotoxicity could contribute to β-cell mass destruction through participation in islet inflammation. We evaluated the potential of empagliflozin (EMPA) and GABA (gamma-aminobutyric acid) to protect β-cell mass against glucotoxicity and to increase β-cell mass after diagnosis of T1D. Empagliflozin is a SGLT2 (sodium-dependent glucose cotransporter) inhibitor which thereby blocks glucose recapture by the kidney and promotes glucose excretion in urine. GABA is an inhibitory neurotransmitter, which stimulates α-to-β cell transdifferentiation. In streptozotocin-treated mice, empagliflozin and/or GABA were delivered for a period of five days or three weeks. As compared to untreated T1D mice, EMPA-treated T1D mice had decreased FFA (free fatty acid) levels and improved glucose homeostasis. EMPA-treated T1D mice had higher islet density, with preserved architecture, compared to T1D mice, and EMPA-treated T1D mice also differed from T1D mice by the total absence of immune cell infiltration within islets. Islets from EMPA-treated mice were also less subjected to ER (endoplasmic reticulum) stress and inflammation, as shown by qPCR analysis. Glucose homeostasis parameters and islet area/pancreas area ratio improved, as compared to diabetic controls, when T1D mice were treated for three weeks with GABA and EMPA. T1D EMPA+GABA mice had higher glucagon levels than T1D mice, without modifications of glucagon area/islet area ratios. In conclusion, empagliflozin and GABA, used in monotherapy in streptozotocin-induced diabetic mice, have positive effects on β-cell mass preservation or proliferation through an indirect effect on islet cell inflammation and ER stress. Further research is mandatory to evaluate whether empagliflozin and GABA may be a potential therapeutic target for the protection of β-cell mass after new-onset T1D.http://dx.doi.org/10.1155/2019/2813489 |
| spellingShingle | Caroline Daems Sophie Welsch Hasnae Boughaleb Juliette Vanderroost Annie Robert Etienne Sokal Philippe A. Lysy Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice Journal of Diabetes Research |
| title | Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice |
| title_full | Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice |
| title_fullStr | Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice |
| title_full_unstemmed | Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice |
| title_short | Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice |
| title_sort | early treatment with empagliflozin and gaba improves β cell mass and glucose tolerance in streptozotocin treated mice |
| url | http://dx.doi.org/10.1155/2019/2813489 |
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