Early Treatment with Empagliflozin and GABA Improves -Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice.
(2019) Journal of Diabetes Research — Vol. 2019, p. 2813489 [1-14] (2019)
Files
EarlytreatmentwithEmpagliflozin.pdf
Open Access - Adobe PDF
- 6.87 MB
Details
- Authors
Daems, Caroline 
Welsch, Sophie Sokal, Etienne
- Abstract
- 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 -cell mass destruction through participation in islet inflammation. We evaluated the potential of empagliflozin (EMPA) and GABA (gamma-aminobutyric acid) to protect -cell mass against glucotoxicity and to increase -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 -to- 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 -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 -cell mass after new-onset T1D.
- Affiliations
Citations
Daems, C., Welsch, S., Boughaleb, H., Vanderroost, J., Robert, A., Sokal, E., & Lysy, P. (2019). Early Treatment with Empagliflozin and GABA Improves -Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice. Journal of Diabetes Research, 2019, 2813489 [1-14]. https://doi.org/10.1155/2019/2813489 (Original work published 2019)