Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes

Louis J. Kolling; Kanza Khan; Nagalakshmi Balasubramanian; Deng-Fu Guo; Kamal Rahmouni; Catherine A. Marcinkiewcz

doi:10.1101/2023.06.12.544498

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Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes

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Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes

Louis J. Kolling, Kanza Khan, Nagalakshmi Balasubramanian, Deng-Fu Guo, Kamal Rahmouni and Catherine A. Marcinkiewcz

bioRxiv

Cold Spring Harbor Laboratory

06/13/2023

DOI: 10.1101/2023.06.12.544498

PMCID: PMC10312607

PMID: 37398179

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https://doi.org/10.1101/2023.06.12.544498View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

In 2020, stay-at-home orders were implemented to stem the spread of SARS-CoV-2 worldwide. Social isolation can be particularly harmful to children and adolescents—during the pandemic, the prevalence of obesity increased by ∼37% in persons aged 2-19. Obesity is often comorbid with type 2 diabetes, which was not assessed in this human pandemic cohort. Here, we investigated whether male mice isolated throughout adolescence develop type 2 diabetes in a manner consistent with human obesity-induced diabetes, and explored neural changes that may underlie such an interaction. We find that isolating C57BL/6J mice throughout adolescence is sufficient to induce type 2 diabetes. We observed fasted hyperglycemia, diminished glucose clearance in response to an insulin tolerance test, decreased insulin signaling in skeletal muscle, decreased insulin staining of pancreatic islets, increased nociception, and diminished plasma cortisol levels compared to group-housed control mice. Using Promethion metabolic phenotyping chambers, we observed dysregulation of sleep and eating behaviors, as well as a time-dependent shift in respiratory exchange ratio of the adolescent-isolation mice. We profiled changes in neural gene transcription from several brain areas and found that a neural circuit between serotonin-producing and GLP-1-producing neurons is affected by this isolation paradigm. Overall, spatial transcription data suggest decreased serotonin neuron activity (via decreased GLP-1-mediated excitation) and increased GLP-1 neuron activity (via decreased serotonin-mediated inhibition). This circuit may represent an intersectional target to further investigate the relationship between social isolation and type 2 diabetes, as well as a pharmacologically-relevant circuit to explore the effects of serotonin and GLP-1 receptor agonists.

Details

Title: Subtitle: Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes
Creators: Louis J. Kolling - University of Iowa
Kanza Khan - Daemen College
Nagalakshmi Balasubramanian - University of Iowa
Deng-Fu Guo - University of Iowa
Kamal Rahmouni - University of Iowa
Catherine A. Marcinkiewcz - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.06.12.544498
PMID: 37398179
PMCID: PMC10312607
Language: English
Date posted: 06/13/2023
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984441854502771

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