Empagliflozin And GABA Improve β-Cell Mass And Glucose Tolerance In New-Onset Type 1 Diabetes
(2019) ATDD (Advances Technologies and Treatments for Diabetes — Location: Berling, Allemagne (20.February.2019)
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- Empagliflozin And GABA Improve β-Cell Mass And Glucose Tolerance In New-Onset Type 1 Diabetes Caroline Daems1*, Sophie Welsch1*, Hasnae Boughaleb1, Juliette Vanderroost1, Annie Robert2, Etienne Sokal1, Philippe A. Lysy1 1Pôle de Pédiatrie, 2Pôle d’Epidémiologie et Biostatistique, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Av. Hippocrate 10, B-1200 Brussels, Belgium *These authors contributed equally to this work, and they are thus sharing first authorship. Presently, the autoimmune character of T1D is challenged, but it is indisputable that inflammation plays a key role in its development. We hypothesized that glucotoxicity could contribute to β-cell mass destruction through maintenance of inflammation. Here, the aim is to evaluate empagliflozin (EMPA) potential to protect β-cell mass against glucotoxicity, and GABA potential to increase the residual β-cell mass after diagnosis of T1D. In a streptozotocin-treated mice model of T1D, empagliflozin and/or GABA were delivered during seven days or three weeks. As compared to untreated T1D mice, EMPA-treated T1D mice had a better glucose homeostasis during tolerance tests and decreased FFA levels. EMPA-treated T1D mice had a better islet density, numbers and preservation of islet architecture, compared to T1D mice. T1D mice showed islet with immune infiltration whereas EMPA-treated T1D mice displayed no islet infiltrate. Islets from EMPA-treated mice were also less subjected to ER stress and inflammation, as shown by qPCR analysis. Furthermore, parameters of glucose homeostasis and β-cell mass were also improved, as compared to diabetic controls, when T1D mice were treated for 3 weeks with GABA and EMPA. Interestingly, T1D EMPA+GABA mice had higher glucagon levels than T1D mice, without modifications of glucagon area/islet area ratios. Empagliflozin and GABA, used in monotherapy, have positive effects on β-cell mass preservation or proliferation through an indirect effect on islet cell inflammation and ER stress. Further researches are mandatory to evaluate whether empagliflozin and GABA may be a potential therapeutic treatment to protect β-cell mass after T1D diagnosis.
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Daems, C., Welsch, S., Boughaleb, H., Vanderroost, J., Robert, A., Sokal, E., & Lysy, P. (2019). Empagliflozin And GABA Improve β-Cell Mass And Glucose Tolerance In New-Onset Type 1 Diabetes. ATDD (Advances Technologies and Treatments for Diabetes, Berling, Allemagne. https://hdl.handle.net/2078.5/228097