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The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease

Type 2 diabetes mellitus increases the risk of sporadic Alzheimer’s disease (sAD), and antidiabetic drugs, including the sodium–glucose cotransporter inhibitors (SGLTI), are being studied as possible sAD therapy. We have explored whether the SGLTI phloridzin may influence metabolic and cognitive par...

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Autores principales: Osmanović Barilar, Jelena, Babić Perhoč, Ana, Knezović, Ana, Homolak, Jan, Virag, Davor, Šalković-Petrišić, Melita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135566/
https://www.ncbi.nlm.nih.gov/pubmed/37189641
http://dx.doi.org/10.3390/biomedicines11041025
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author Osmanović Barilar, Jelena
Babić Perhoč, Ana
Knezović, Ana
Homolak, Jan
Virag, Davor
Šalković-Petrišić, Melita
author_facet Osmanović Barilar, Jelena
Babić Perhoč, Ana
Knezović, Ana
Homolak, Jan
Virag, Davor
Šalković-Petrišić, Melita
author_sort Osmanović Barilar, Jelena
collection PubMed
description Type 2 diabetes mellitus increases the risk of sporadic Alzheimer’s disease (sAD), and antidiabetic drugs, including the sodium–glucose cotransporter inhibitors (SGLTI), are being studied as possible sAD therapy. We have explored whether the SGLTI phloridzin may influence metabolic and cognitive parameters in a rat model of sAD. Adult male Wistar rats were randomized to a control (CTR), an sAD-model group induced by intracerebroventricular streptozotocin (STZ-icv; 3 mg/kg), a CTR+SGLTI, or an STZ-icv+SGLTI group. Two-month-long oral (gavage) SGLTI treatment (10 mg/kg) was initiated 1 month after STZ-icv and cognitive performance tested prior to sacrifice. SGLTI treatment significantly decreased plasma glucose levels only in the CTR group and failed to correct STZ-icv-induced cognitive deficit. In both the CTR and STZ-icv groups, SGLTI treatment diminished weight gain, decreased amyloid beta (Aβ) 1-42 in duodenum, and decreased the plasma levels of total glucagon-like peptide 1 (GLP-1), while the levels of active GLP-1, as well as both total and active glucose-dependent insulinotropic polypeptide, remained unchanged, compared to their respective controls. The increment in GLP-1 levels in the cerebrospinal fluid and its effect on Aβ 1-42 in duodenum could be one of the molecular mechanisms by which SGLTIs indirectly induce pleiotropic beneficial effects.
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spelling pubmed-101355662023-04-28 The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease Osmanović Barilar, Jelena Babić Perhoč, Ana Knezović, Ana Homolak, Jan Virag, Davor Šalković-Petrišić, Melita Biomedicines Article Type 2 diabetes mellitus increases the risk of sporadic Alzheimer’s disease (sAD), and antidiabetic drugs, including the sodium–glucose cotransporter inhibitors (SGLTI), are being studied as possible sAD therapy. We have explored whether the SGLTI phloridzin may influence metabolic and cognitive parameters in a rat model of sAD. Adult male Wistar rats were randomized to a control (CTR), an sAD-model group induced by intracerebroventricular streptozotocin (STZ-icv; 3 mg/kg), a CTR+SGLTI, or an STZ-icv+SGLTI group. Two-month-long oral (gavage) SGLTI treatment (10 mg/kg) was initiated 1 month after STZ-icv and cognitive performance tested prior to sacrifice. SGLTI treatment significantly decreased plasma glucose levels only in the CTR group and failed to correct STZ-icv-induced cognitive deficit. In both the CTR and STZ-icv groups, SGLTI treatment diminished weight gain, decreased amyloid beta (Aβ) 1-42 in duodenum, and decreased the plasma levels of total glucagon-like peptide 1 (GLP-1), while the levels of active GLP-1, as well as both total and active glucose-dependent insulinotropic polypeptide, remained unchanged, compared to their respective controls. The increment in GLP-1 levels in the cerebrospinal fluid and its effect on Aβ 1-42 in duodenum could be one of the molecular mechanisms by which SGLTIs indirectly induce pleiotropic beneficial effects. MDPI 2023-03-27 /pmc/articles/PMC10135566/ /pubmed/37189641 http://dx.doi.org/10.3390/biomedicines11041025 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Osmanović Barilar, Jelena
Babić Perhoč, Ana
Knezović, Ana
Homolak, Jan
Virag, Davor
Šalković-Petrišić, Melita
The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease
title The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease
title_full The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease
title_fullStr The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease
title_full_unstemmed The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease
title_short The Effect of the Sodium—Glucose Cotransporter Inhibitor on Cognition and Metabolic Parameters in a Rat Model of Sporadic Alzheimer’s Disease
title_sort effect of the sodium—glucose cotransporter inhibitor on cognition and metabolic parameters in a rat model of sporadic alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135566/
https://www.ncbi.nlm.nih.gov/pubmed/37189641
http://dx.doi.org/10.3390/biomedicines11041025
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