The effect of spermidine on autoimmunity and beta cell function in NOD mice

Abstract Spermidine is a natural polyamine which was shown to prolong lifespan of organisms and to improve cardiac and cognitive function. Spermidine was also reported to reduce inflammation and modulate T-cells. Autophagy is one of the mechanisms that spermidine exerts its effect. Autophagy is vita...

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Main Authors: Ceren Karacay, Barbara Prietl, Clemens Harer, Barbara Ehall, Christoph W. Haudum, Kaddour Bounab, Joakim Franz, Tobias Eisenberg, Frank Madeo, Dagmar Kolb, Kerstin Hingerl, Markus Hausl, Christoph Magnes, Selma I. Mautner, Petra Kotzbeck, Thomas R. Pieber
Format: Article
Language:English
Published: Nature Portfolio 2022-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-08168-2
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author Ceren Karacay
Barbara Prietl
Clemens Harer
Barbara Ehall
Christoph W. Haudum
Kaddour Bounab
Joakim Franz
Tobias Eisenberg
Frank Madeo
Dagmar Kolb
Kerstin Hingerl
Markus Hausl
Christoph Magnes
Selma I. Mautner
Petra Kotzbeck
Thomas R. Pieber
author_facet Ceren Karacay
Barbara Prietl
Clemens Harer
Barbara Ehall
Christoph W. Haudum
Kaddour Bounab
Joakim Franz
Tobias Eisenberg
Frank Madeo
Dagmar Kolb
Kerstin Hingerl
Markus Hausl
Christoph Magnes
Selma I. Mautner
Petra Kotzbeck
Thomas R. Pieber
author_sort Ceren Karacay
collection DOAJ
description Abstract Spermidine is a natural polyamine which was shown to prolong lifespan of organisms and to improve cardiac and cognitive function. Spermidine was also reported to reduce inflammation and modulate T-cells. Autophagy is one of the mechanisms that spermidine exerts its effect. Autophagy is vital for β-cell homeostasis and autophagy deficiency was reported to lead to exacerbated diabetes in mice. The effect of spermidine in type 1 diabetes pathogenesis remains to be elucidated. Therefore, we examined the effect of spermidine treatment in non-obese diabetic (NOD) mice, a mouse model for type 1 diabetes. NOD mice were given untreated or spermidine-treated water ad libitum from 4 weeks of age until diabetes onset or 35 weeks of age. We found that treatment with 10 mM spermidine led to higher diabetes incidence in NOD mice despite unchanged pancreatic insulitis. Spermidine modulated tissue polyamine levels and elevated signs of autophagy in pancreas. Spermidine led to increased proportion of pro-inflammatory T-cells in pancreatic lymph nodes (pLN) in diabetic mice. Spermidine elevated the proportion of regulatory T-cells in early onset mice, whereas it reduced the proportion of regulatory T-cells in late onset mice. In summary spermidine treatment led to higher diabetes incidence and elevated proportion of T-cells in pLN.
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spelling doaj.art-71b4df741d6549db8fd46ce95bd7c38f2022-12-21T21:10:31ZengNature PortfolioScientific Reports2045-23222022-03-0112111410.1038/s41598-022-08168-2The effect of spermidine on autoimmunity and beta cell function in NOD miceCeren Karacay0Barbara Prietl1Clemens Harer2Barbara Ehall3Christoph W. Haudum4Kaddour Bounab5Joakim Franz6Tobias Eisenberg7Frank Madeo8Dagmar Kolb9Kerstin Hingerl10Markus Hausl11Christoph Magnes12Selma I. Mautner13Petra Kotzbeck14Thomas R. Pieber15Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazBioTechMed GrazBioTechMed GrazCore Facility Ultrastructure Analysis, Center for Medical Research (ZMF), Medical University of GrazCore Facility Ultrastructure Analysis, Center for Medical Research (ZMF), Medical University of GrazJoanneum Research Forschungsgesellschaft mbH HEALTH – Institute for Biomedicine and Health SciencesJoanneum Research Forschungsgesellschaft mbH HEALTH – Institute for Biomedicine and Health SciencesDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazDivision of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of GrazAbstract Spermidine is a natural polyamine which was shown to prolong lifespan of organisms and to improve cardiac and cognitive function. Spermidine was also reported to reduce inflammation and modulate T-cells. Autophagy is one of the mechanisms that spermidine exerts its effect. Autophagy is vital for β-cell homeostasis and autophagy deficiency was reported to lead to exacerbated diabetes in mice. The effect of spermidine in type 1 diabetes pathogenesis remains to be elucidated. Therefore, we examined the effect of spermidine treatment in non-obese diabetic (NOD) mice, a mouse model for type 1 diabetes. NOD mice were given untreated or spermidine-treated water ad libitum from 4 weeks of age until diabetes onset or 35 weeks of age. We found that treatment with 10 mM spermidine led to higher diabetes incidence in NOD mice despite unchanged pancreatic insulitis. Spermidine modulated tissue polyamine levels and elevated signs of autophagy in pancreas. Spermidine led to increased proportion of pro-inflammatory T-cells in pancreatic lymph nodes (pLN) in diabetic mice. Spermidine elevated the proportion of regulatory T-cells in early onset mice, whereas it reduced the proportion of regulatory T-cells in late onset mice. In summary spermidine treatment led to higher diabetes incidence and elevated proportion of T-cells in pLN.https://doi.org/10.1038/s41598-022-08168-2
spellingShingle Ceren Karacay
Barbara Prietl
Clemens Harer
Barbara Ehall
Christoph W. Haudum
Kaddour Bounab
Joakim Franz
Tobias Eisenberg
Frank Madeo
Dagmar Kolb
Kerstin Hingerl
Markus Hausl
Christoph Magnes
Selma I. Mautner
Petra Kotzbeck
Thomas R. Pieber
The effect of spermidine on autoimmunity and beta cell function in NOD mice
Scientific Reports
title The effect of spermidine on autoimmunity and beta cell function in NOD mice
title_full The effect of spermidine on autoimmunity and beta cell function in NOD mice
title_fullStr The effect of spermidine on autoimmunity and beta cell function in NOD mice
title_full_unstemmed The effect of spermidine on autoimmunity and beta cell function in NOD mice
title_short The effect of spermidine on autoimmunity and beta cell function in NOD mice
title_sort effect of spermidine on autoimmunity and beta cell function in nod mice
url https://doi.org/10.1038/s41598-022-08168-2
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