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(D-Ser2)Oxm[Lys38-γ-glu-PAL] improves hippocampal gene expression and cognitionin a mouse model of type 1 diabetes

Pathak, NM, Irwin, Nigel, Pathak, V, Gault, Victor A and Flatt, Peter (2016) (D-Ser2)Oxm[Lys38-γ-glu-PAL] improves hippocampal gene expression and cognitionin a mouse model of type 1 diabetes. Journal of Experimental and Integrative Medicine, 6 (1). pp. 1-5. [Journal article]

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URL: http://www.scopemed.org/?mno=215201

DOI: 10.5455/jeim.050216.br.027

Abstract

Objective: Oxyntomodulin (Oxm) is a gastrointestinal hormone with recently noted therapeutic potential for type 1 diabetes mellitus (T1DM). The present study examined the effects of a stable Oxm analogue on anxiety, exploratory behavior, cognitive function, hippocampal gene expression and metabolic control in a mouse model of T1DM. Methods: Effects of twice daily administration of the stable Oxm analogue, (d-Ser2)Oxm[Lys38-γ-glu-PAL], was assessed in insulin-deficient streptozotocin (STZ)-induced T1DM mice. Results: Induction of diabetes by STZ injection significantly (P < 0.05) impaired learning and memory compared to normal control mice. However, (d-Ser2)Oxm[Lys38-γ-glu-PAL] treatment completely reversed this detrimental effect. Anxiety levels and exploratory behavior were not significantly different between all groups of mice. Hippocampal gene expression of MASH1, SYP and mTOR were reduced (P < 0.01 to P < 0.001) in T1DM mice, but significantly (P < 0.05 to P < 0.001) enhanced by twice daily (d-Ser2)Oxm[Lys38- γ-glu-PAL] intervention. Moreover, expression of SYP, mTOR and IRS-1 were significantly elevated (P < 0.05 to P < 0.001) in (d-Ser2)Oxm[Lys38-γ-glu-PAL] mice compared to both STZ and lean controls. These effects were accompanied by improved (P < 0.001) glucose tolerance and insulin sensitivity compared to STZ controls. Conclusion: The data highlight the potential of (d-Ser2)Oxm[Lys38-γ-glu-PAL] for the treatment of T1DM, and reveal the ability of this Oxm analogue to restore the deficits of learning and memory observed in STZ-induced T1DM.

Item Type:Journal article
Keywords:Oxyntomodulin; hippocampus; cognitive function, type 1 diabetes
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
Biomedical Sciences Research Institute > Diabetes
ID Code:34512
Deposited By: Dr Nigel Irwin
Deposited On:26 Apr 2016 09:25
Last Modified:14 Nov 2016 16:34

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