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Role of the Gut-Islet Axis in and Beyond Metabolic Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 3143

Editor


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Guest Editor
1. Department of Diabetes, Nutrition and Metabolic Diseases, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
2. Clinic of Diabetes, Nutrition and Metabolic Diseases, Emergency County Hospital, 200642 Craiova, Romania
Interests: metabolic diseases epidemiology; biochemical and molecular biomarkers of obesity and diabetes; entero-insular axis; insulinresistance; obesity cardio-metabolic phenotypes
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Special Issue Information

Dear Colleagues,

Metabolic diseases represent a major challenge and a public health problem worldwide, causing serious adverse health outcomes and comorbidities. Incretins are increasingly studied for their dual metabolic and neuroprotective actions, offering a bridge between weight regulation and neurodegeneration.

In recent years, the role of entero-insular axis as a critical factor in the metabolic changes associated with aging, have received great interest, driving the need for targeted therapies that are effective in the context of the age-related metabolic disturbances. Currently, modulation of the gut–islet axis is recognized as not only a metabolic therapy but also a neuropharmacological therapy, reflecting their expanding use in obesity and diabetes and the growing evidence of brain effects. Although clinical observations show concurrent weight loss and neuroprotection, isolated reports of depressive symptoms have emerged, necessitating a clearer understanding of their central safety profile.

This Special Issue will be dedicated to the molecular and mechanistic perspective of the gut–islet axis, focusing on incretin signaling pathways, receptor-mediated mechanisms and the molecular regulation of metabolic and pleiotropic effects. Key topics include the molecular mechanisms of weight loss, differentiating between central satiety signaling and peripheral gastric effects; the role of incretins in modulating the glucose, lipid and metabolic-associated fatty liver disease effects; the influence of neurotransmitter modulation on energy balance, food intake and the neuroprotective potential of incretins.

Dr. Simona Georgiana Popa
Guest Editor

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Keywords

  • entero-insular axis
  • adipocytokines
  • precision therapy
  • insulin resistance
  • type 2 diabetes
  • neuroprotection
  • aging

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Published Papers (1 paper)

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Review

29 pages, 488 KB  
Review
Glucagon-like Peptide-1 and Dual GIP/GLP-1 Receptor Agonists in Brain: Exploring the Expanding Role and Safety in Neuropsychiatry
by Ana Cristina Tudosie, Loredana-Maria Marin, Simona Georgiana Popa and Andreea Loredana Golli
Int. J. Mol. Sci. 2026, 27(8), 3628; https://doi.org/10.3390/ijms27083628 - 18 Apr 2026
Viewed by 2912
Abstract
Glucagon-like peptide-1 (GLP-1) and dual GIP/GLP-1 receptor agonists, originally introduced for the management of type 2 diabetes mellitus and obesity, are increasingly recognized for their broader actions within the central nervous system, with emerging implications in neuropsychiatry and neurodegeneration. This review integrates current [...] Read more.
Glucagon-like peptide-1 (GLP-1) and dual GIP/GLP-1 receptor agonists, originally introduced for the management of type 2 diabetes mellitus and obesity, are increasingly recognized for their broader actions within the central nervous system, with emerging implications in neuropsychiatry and neurodegeneration. This review integrates current preclinical and clinical evidence, emphasizing their pharmacodynamic profile, central receptor distribution, and the molecular pathways linking metabolic signaling to neural function. Evidence suggests that GLP-1 receptor activation across key brain regions involved in energy balance and reward modulates multiple neurotransmitter systems, including dopamine and serotonin, as well as glutamatergic and GABAergic transmission, thereby influencing behavior, affective processes, and cognitive function. In parallel, these agents exhibit neuroprotective properties through improved neuronal insulin sensitivity, attenuation of neuroinflammatory pathways, and support of neuroplasticity, alongside effects on limiting pathological protein aggregation. Dual GIP/GLP-1 agonism may further potentiate these central actions through complementary metabolic and synaptic mechanisms. Although pharmacovigilance data have identified isolated neuropsychiatric adverse events, current clinical evidence does not support a consistent causal association. Collectively, incretin-based therapies represent a promising translational approach at the interface of metabolic and neuropsychiatric disorders, warranting further investigation into their long-term central safety, therapeutic efficacy, and clinical relevance. Full article
(This article belongs to the Special Issue Role of the Gut-Islet Axis in and Beyond Metabolic Diseases)
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