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Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?

The tryptophan–kynurenine pathway (Trp–KYN) is the major route for tryptophan conversion in the brain and in the periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. The net ef...

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Autores principales: Kozieł, Kamila, Urbanska, Ewa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913876/
https://www.ncbi.nlm.nih.gov/pubmed/36766803
http://dx.doi.org/10.3390/cells12030460
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author Kozieł, Kamila
Urbanska, Ewa M.
author_facet Kozieł, Kamila
Urbanska, Ewa M.
author_sort Kozieł, Kamila
collection PubMed
description The tryptophan–kynurenine pathway (Trp–KYN) is the major route for tryptophan conversion in the brain and in the periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. The net effect depends on their local concentration, cellular environment, as well as a complex positive and negative feedback loops. The imbalance between beneficial and harmful kynurenines was implicated in the pathogenesis of various neurodegenerative disorders, psychiatric illnesses and metabolic disorders, including diabetes mellitus (DM). Despite available therapies, DM may lead to serious macro- and microvascular complications including cardio- and cerebrovascular disease, peripheral vascular disease, chronic renal disease, diabetic retinopathy, autonomic neuropathy or cognitive impairment. It is well established that low-grade inflammation, which often coincides with DM, can affect the function of KP and, conversely, that kynurenines may modulate the immune response. This review provides a detailed summary of findings concerning the status of the Trp–KYN pathway in DM based on available animal, human and microbiome studies. We highlight the importance of the molecular interplay between the deranged (functionally and qualitatively) conversion of Trp to kynurenines in the development of DM and insulin resistance. The Trp–KYN pathway emerges as a novel target in the search for preventive and therapeutic interventions in DM.
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spelling pubmed-99138762023-02-11 Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target? Kozieł, Kamila Urbanska, Ewa M. Cells Review The tryptophan–kynurenine pathway (Trp–KYN) is the major route for tryptophan conversion in the brain and in the periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic/cytoprotective, oxidant/antioxidant or pro-/anti-inflammatory. The net effect depends on their local concentration, cellular environment, as well as a complex positive and negative feedback loops. The imbalance between beneficial and harmful kynurenines was implicated in the pathogenesis of various neurodegenerative disorders, psychiatric illnesses and metabolic disorders, including diabetes mellitus (DM). Despite available therapies, DM may lead to serious macro- and microvascular complications including cardio- and cerebrovascular disease, peripheral vascular disease, chronic renal disease, diabetic retinopathy, autonomic neuropathy or cognitive impairment. It is well established that low-grade inflammation, which often coincides with DM, can affect the function of KP and, conversely, that kynurenines may modulate the immune response. This review provides a detailed summary of findings concerning the status of the Trp–KYN pathway in DM based on available animal, human and microbiome studies. We highlight the importance of the molecular interplay between the deranged (functionally and qualitatively) conversion of Trp to kynurenines in the development of DM and insulin resistance. The Trp–KYN pathway emerges as a novel target in the search for preventive and therapeutic interventions in DM. MDPI 2023-01-31 /pmc/articles/PMC9913876/ /pubmed/36766803 http://dx.doi.org/10.3390/cells12030460 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kozieł, Kamila
Urbanska, Ewa M.
Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?
title Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?
title_full Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?
title_fullStr Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?
title_full_unstemmed Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?
title_short Kynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?
title_sort kynurenine pathway in diabetes mellitus—novel pharmacological target?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913876/
https://www.ncbi.nlm.nih.gov/pubmed/36766803
http://dx.doi.org/10.3390/cells12030460
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