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

NM Pathak, Nigel Irwin, V Pathak, Victor A Gault, Peter Flatt

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages1-5
JournalJournal of Experimental and Integrative Medicine
Volume6
Issue number1
DOIs
Publication statusPublished - 30 May 2016

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Oxyntomodulin
Type 1 Diabetes Mellitus
Gene Expression
Streptozocin
Exploratory Behavior
Anxiety
Learning
Gastrointestinal Hormones
D-Ser2-oxyntomodulin
Aptitude
Experimental Diabetes Mellitus
Memory Disorders
Cognition
Insulin Resistance
Therapeutics

Keywords

  • Oxyntomodulin
  • hippocampus
  • cognitive function
  • type 1 diabetes

Cite this

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title = "(D-Ser2)Oxm[Lys38-γ-glu-PAL] improves hippocampal gene expression and cognitionin a mouse model of type 1 diabetes",
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.",
keywords = "Oxyntomodulin, hippocampus, cognitive function, type 1 diabetes",
author = "NM Pathak and Nigel Irwin and V Pathak and Gault, {Victor A} and Peter Flatt",
year = "2016",
month = "5",
day = "30",
doi = "10.5455/jeim.050216.br.027",
language = "English",
volume = "6",
pages = "1--5",
journal = "Journal of Experimental and Integrative Medicine",
issn = "1309-4572",
number = "1",

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TY - JOUR

T1 - (D-Ser2)Oxm[Lys38-γ-glu-PAL] improves hippocampal gene expression and cognitionin a mouse model of type 1 diabetes

AU - Pathak, NM

AU - Irwin, Nigel

AU - Pathak, V

AU - Gault, Victor A

AU - Flatt, Peter

PY - 2016/5/30

Y1 - 2016/5/30

N2 - 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.

AB - 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.

KW - Oxyntomodulin

KW - hippocampus

KW - cognitive function

KW - type 1 diabetes

U2 - 10.5455/jeim.050216.br.027

DO - 10.5455/jeim.050216.br.027

M3 - Article

VL - 6

SP - 1

EP - 5

JO - Journal of Experimental and Integrative Medicine

T2 - Journal of Experimental and Integrative Medicine

JF - Journal of Experimental and Integrative Medicine

SN - 1309-4572

IS - 1

ER -