Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice
Joint Authors
Lysy, Philippe A.
Sokal, Etienne
Daems, Caroline
Welsch, Sophie
Boughaleb, Hasnae
Vanderroost, Juliette
Robert, A.
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-07-30
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Daems, Caroline& Welsch, Sophie& Boughaleb, Hasnae& Vanderroost, Juliette& Robert, A.& Sokal, Etienne…[et al.]. 2019. Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice. Journal of Diabetes Research،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1172855
Modern Language Association (MLA)
Daems, Caroline…[et al.]. Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice. Journal of Diabetes Research No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1172855
American Medical Association (AMA)
Daems, Caroline& Welsch, Sophie& Boughaleb, Hasnae& Vanderroost, Juliette& Robert, A.& Sokal, Etienne…[et al.]. Early Treatment with Empagliflozin and GABA Improves β-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice. Journal of Diabetes Research. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1172855
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1172855