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Long-term effects of l-serine supplementation upon a mouse model of diabetic neuropathy

Xia, Chuying; Suriyanarayanan, Saranya; Gong, Yi; Fridman, Vera; Selig, Martin; Li, Jia; Rutkove, Seward; Hornemann, Thorsten; Eichler, Florian (2023). Long-term effects of l-serine supplementation upon a mouse model of diabetic neuropathy. Journal of Diabetes and Its Complications, 37(2):108383.

Abstract

Deoxysphingolipids (1-deoxySLs) are neurotoxic sphingolipids associated with obesity and diabetic neuropathy (DN) and have been linked to severity of functional peripheral neuropathies. While l-serine supplementation can reduce 1-deoxySL accumulation and improve insulin sensitivity and sensory nerve velocity, long-term outcomes have not yet been examined. To assess this, we treated 2 month old db/db mice, a model of DN, with 5-20 % oral l-serine for 6 months and longitudinally quantified the extent of functional neuropathy progression. We examined putative biomarkers of neuropathy in blood and tissue and quantified levels of small fiber neuropathy, looking for associations between lowered 1-deoxySL and phenotypes. Toxic 1-deoxySLs were suppressed long-term in plasma and various tissue including the sciatic nerve, which is particularly targeted in DN. Functional neuropathy and sensory modalities were significantly improved in the treatment group well into advanced stages of disease. However, structural assessments revealed prominent axonal degeneration, apoptosis and Schwann cell pathology, suggesting that neuropathy was ongoing. Hyperglycemia and dyslipidemia persisted during our study, and high levels of glutathione were seen in the spinal cord. Our results demonstrate that despite significant functional improvements, l-serine does not prevent chronic degenerative changes specifically at the structural level, pointing to other processes such as oxidative damage and hyperglycemia, that persist despite 1-deoxySL reduction.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
Dewey Decimal Classification:610 Medicine & health
540 Chemistry
Scopus Subject Areas:Health Sciences > Internal Medicine
Health Sciences > Endocrinology, Diabetes and Metabolism
Life Sciences > Endocrinology
Language:English
Date:February 2023
Deposited On:22 Mar 2023 13:33
Last Modified:29 Oct 2024 02:39
Publisher:Elsevier
ISSN:1056-8727
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.jdiacomp.2022.108383
PubMed ID:36610321

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