Skip to content

Study · Animal study (in vivo) · mouse · 2026

3 results

Immunometabolic dysregulation drives selective executive cognitive dysfunction in male db/db mice.

Alasousi D, Braysh K, D'Souza L, Islam S, Alhawaj F, Nizam R, John S, Williams MR, Albuloushi A, Altarrah D, Al-Hussaini H, Carare RO, Al-Mulla F, Alzaid F, Al-Onaizi M

Neurobiology of disease1 Apr 2026

PMID41933665 (opens in a new tab)DOI10.1016/j.nbd.2026.107376 (opens in a new tab)PepBankPUB-41933665
Publisher pagePubMedAsk about this study
Jump to 3 results

Summary

Type 2 diabetes (T2D) is associated with cognitive impairment, with executive functions such as cognitive flexibility being particularly vulnerable. Growing evidence suggests that chronic inflammatory and metabolic stress contributes to diabetes -related brain dysfunction, yet behavioral assessment in animal models is often confounded by anxiety, altered motivation, and reduced response vigor. In this study, we used a translational touchscreen-based operant platform to distinguish associative learning from executive cognitive flexibility in db/db mice, a well-established genetic model of T2D, and to evaluate the effects of the non-erythropoietic erythropoietin derived peptide ARA 290. Male db/db mice and age matched db/m heterozygote lean controls were tested using pairwise visual discrimination to assess associative learning and reversal learning to probe cognitive flexibility. Metabolic function was evaluated using glucose and insulin tolerance tests, while immune and metabolic effects of ARA 290 were evaluated by flow cytometry and RNA-seq. Db/db mice displayed delayed task engagement and longer response latencies during pretraining and acquisition, yet maintained intact associative learning accuracy. In contrast, they exhibited pronounced impairments in cognitive flexibility during reversal learning, characterized by increased perseveration and reduced adaptation to changed reward contingencies. Treatment with ARA 290 improved insulin sensitivity and altered circulating monocyte proportions but did not rescue deficits in executive cognitive flexibility. RNA-seq of the hippocampus revealed enrichment of immune pathways consistent with chronic low-grade inflammation, providing molecular context for the observed behavioral phenotype. Together, these findings demonstrate that T2D selectively impairs executive cognitive flexibility while sparing basic associative learning, and that improvement in peripheral metabolic function and altered monocyte proportions are insufficient to restore executive cognition. This work highlights the value of touchscreen-based paradigms for resolving distinct cognitive domains in metabolic disease and highlights the need to target brain specific immunometabolic mechanisms to address diabetes-associated cognitive dysfunction.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In db/db mice, treatment with ARA‑290 improved insulin sensitivity.

    In plain wordsIn mice with type 2 diabetes, ARA‑290 improved insulin sensitivity.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    IncreaseInsulin sensitivity
    Study

    mousen: not reported in source

    db/db mice (type 2 diabetes model)
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Treatment with ARA 290 improved insulin sensitivity and altered circulating monocyte proportions but did not rescue deficits in executive cognitive flexibility.
    2 context sentences
    Summary · context
    Male db/db mice and age matched db/m heterozygote lean controls were tested using pairwise visual discrimination to assess associative learning and reversal learning to probe cognitive flexibility.
    Summary · context
    Metabolic function was evaluated using glucose and insulin tolerance tests, while immune and metabolic effects of ARA 290 were evaluated by flow cytometry and RNA-seq.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In db/db mice, treatment with ARA‑290 altered circulating monocyte proportions; the abstract does not state the direction.

    In plain wordsIn mice with type 2 diabetes, ARA‑290 changed the share of monocytes (a white blood cell type) in the blood.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    Direction not reportedCirculating monocyte proportions
    Study

    mousen: not reported in source

    db/db mice (type 2 diabetes model)
    Outcome group
    Immune response · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Treatment with ARA 290 improved insulin sensitivity and altered circulating monocyte proportions but did not rescue deficits in executive cognitive flexibility.
    2 context sentences
    Summary · context
    Male db/db mice and age matched db/m heterozygote lean controls were tested using pairwise visual discrimination to assess associative learning and reversal learning to probe cognitive flexibility.
    Summary · context
    Metabolic function was evaluated using glucose and insulin tolerance tests, while immune and metabolic effects of ARA 290 were evaluated by flow cytometry and RNA-seq.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In db/db mice, treatment with ARA‑290 did not rescue deficits in executive cognitive flexibility.

    In plain wordsIn mice with type 2 diabetes, ARA‑290 did not restore their impaired mental flexibility.

    Peptide
    Cibinetide (ARA-290)
    Outcome
    No significant changeExecutive cognitive flexibility (reversal learning)
    Study

    mousen: not reported in source

    db/db mice (type 2 diabetes model)
    Outcome group
    Cognition and memory · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Treatment with ARA 290 improved insulin sensitivity and altered circulating monocyte proportions but did not rescue deficits in executive cognitive flexibility.
    2 context sentences
    Summary · context
    Male db/db mice and age matched db/m heterozygote lean controls were tested using pairwise visual discrimination to assess associative learning and reversal learning to probe cognitive flexibility.
    Summary · context
    Metabolic function was evaluated using glucose and insulin tolerance tests, while immune and metabolic effects of ARA 290 were evaluated by flow cytometry and RNA-seq.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 19:08 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:13 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

PepBank is a research reference. Talk to a doctor before you use any peptide.