Different impacts of acylated and non-acylated long-acting insulin analogs on neural functions in vitro and in vivo

Diabetes Research and Clinical Practice
Hiroshi TsunekiToshiyasu Sasaoka

Abstract

Centrally administered insulin improves cognitive functions in patients with Alzheimer's disease; however, it remains unknown whether long-acting insulin analogs exert more pronounced effects than insulin. In the present study, we directly compared the effects of insulin and its analogs on neural functions in vitro and in vivo. Cultured rat cerebral cortical neurons were treated with insulin, insulin glargine U100 (Gla), insulin detemir (Det), or insulin degludec (Deg). Moreover, these drugs were intracerebroventricularly administered to mice. Their efficacies were evaluated by biochemical and behavioral analyses. In cultured neurons, insulin, Gla, and Det increased phosphorylation of Akt and enhanced gene expression of brain-derived neurotrophic factor to a similar extent, although Deg was less effective. The effects of Det and Deg, but not insulin and Gla were suppressed by addition of albumin. When the drug was centrally administered, the increasing effects of insulin on the Akt phosphorylation were comparable to those of Gla but greater than those of Det in hippocampus and cerebral cortex of diabetic db/db and non-diabetic db/m+ mice. Moreover, insulin and Gla enhanced memory functions in Y-maze test and suppressed depressi...Continue Reading

Citations

Apr 14, 2020·Cell Proliferation·Xiao Han ZouRan Ji Cui
Mar 21, 2019·World Journal of Diabetes·Eleni XourgiaAndreas Melidonis
Dec 15, 2020·Neuroscience Research·Tomofumi Watanabe, Kazuhiro Sakamoto
Aug 25, 2021·Molecular Metabolism·Mark A JarosinskiMichael A Weiss
Dec 2, 2021·The Journal of Clinical Endocrinology and Metabolism·Mark A JarosinskiMichael A Weiss

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