Vildagliptin, a DPP4 Inhibitor, Alleviates Diabetes-associated Cognitive Deficits by Decreasing the Levels of Apoptosis-related Proteins in the Rat Hippocampus

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2018 May 29

PMID 29805536

Citations 15

Authors

Dan-Dan Zhang

Nan Shi

Hui Fang

Liang Ma

Wei-Ping Wu

Ya-Zhong Zhang

Jin-Li Tian

Luo-Bing Tian

Kang Kang

Si Chen

Affiliations

Soon will be listed here.

Abstract

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3β signaling pathway.

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