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Combination of Insulin with a GLP1 Agonist Is Associated with Better Memory and Normal Expression of Insulin Receptor Pathway Genes in a Mouse Model of Alzheimer's Disease.

TitleCombination of Insulin with a GLP1 Agonist Is Associated with Better Memory and Normal Expression of Insulin Receptor Pathway Genes in a Mouse Model of Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2019
AuthorsRobinson A, Lubitz I, Atrakchi-Baranes D, Licht-Murava A, Katsel P, Leroith D, Liraz-Zaltsman S, Haroutunian V, Beeri MSchnaider
JournalJ Mol Neurosci
Date Published2019 Jan 11
ISSN1559-1166
Abstract

Disruption of brain insulin signaling may explain the higher Alzheimer's disease (AD) risk among type 2 diabetic (T2D) patients. There is evidence from in vitro and human postmortem studies that combination of insulin with hypoglycemic medications is neuroprotective and associated with less amyloid aggregation. We examined the effect of 8-month intranasal administration of insulin, exenatide (a GLP-1 agonist), combination therapy (insulin + exenatide) or saline, in wild-type (WT) and an AD-like mouse model (Tg2576). Mice were assessed for learning, gene expression of key mediators and effectors of the insulin receptor signaling pathway (IRSP-IRS1, AKT1, CTNNB1, INSR, IRS2, GSK3B, IGF1R, AKT3), and brain Amyloid Beta (Aβ) levels. In Tg2576 mice, combination therapy reduced expression of IRSP genes which was accompanied by better learning. Cortical Aβ levels were decreased by 15-30% in all groups compared to saline but this difference did not reach statistical significance. WT mice groups, with or without treatment, did not differ in any comparison. Disentangling the mechanisms underlying the potential beneficial effects of combination therapy on the IR pathway and AD-like behavior is warranted.

DOI10.1007/s12031-019-1257-9
Alternate JournalJ. Mol. Neurosci.
PubMed ID30635783
Grant ListRO1 AG034087 / / National Institutes of Health /
RO1 AG051545 / / National Institutes of Health /
1I01BX002267 / / VA Merit /
01 / / Leroy Schecter Foundation /
01 / / Bader Philanthropies /