Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)

<b>Aims and Background:</b> Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is p...

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Main Authors: Julia Fischer, Nina Judith Hos, Sophie Tritschler, Joel Schmitz-Peters, Raja Ganesan, Chiara Calabrese, Petra Schiller, Hannah Brunnert, Angela Nowag, Sandra Winter, Ruth Hanßen, Katja Römer, Nazifa Qurishi, Isabelle Suarèz, Norma Jung, Clara Lehmann, Georg Plum, Michael Faust, Pia Hartmann, Nirmal Robinson
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Diabetology
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Online Access:https://www.mdpi.com/2673-4540/6/6/45
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author Julia Fischer
Nina Judith Hos
Sophie Tritschler
Joel Schmitz-Peters
Raja Ganesan
Chiara Calabrese
Petra Schiller
Hannah Brunnert
Angela Nowag
Sandra Winter
Ruth Hanßen
Katja Römer
Nazifa Qurishi
Isabelle Suarèz
Norma Jung
Clara Lehmann
Georg Plum
Michael Faust
Pia Hartmann
Nirmal Robinson
author_facet Julia Fischer
Nina Judith Hos
Sophie Tritschler
Joel Schmitz-Peters
Raja Ganesan
Chiara Calabrese
Petra Schiller
Hannah Brunnert
Angela Nowag
Sandra Winter
Ruth Hanßen
Katja Römer
Nazifa Qurishi
Isabelle Suarèz
Norma Jung
Clara Lehmann
Georg Plum
Michael Faust
Pia Hartmann
Nirmal Robinson
author_sort Julia Fischer
collection DOAJ
description <b>Aims and Background:</b> Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 (SIRT1) plays an important role in regulating cellular metabolism, including T2DM and aging. Furthermore, we have recently demonstrated that SIRT1 critically regulates inflammatory pathways and autophagy during infection. Thus, we aimed to investigate SIRT1 expression and its correlation with autophagy in peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic patients. <b>Methods:</b> Clinical characteristics of the study subjects were obtained. SIRT1 and autophagic markers such as p62 and LC3-I/II were determined using Western blot analysis followed by densitometric analysis. <b>Results:</b> We found that SIRT1 levels were decreased in PBMCs of diabetic patients in an age-dependent manner. Importantly, reduced SIRT1 expression correlated with reduced LC3-II/I ratios, indicating reduced autophagy. Reduced SIRT1 also corresponded to decreased autophagic adaptor protein Sequestome-1/p62. <b>Conclusions:</b> In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients.
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spelling doaj-art-49def5b8ec514eeb80fa300be8301ea62025-08-20T02:24:21ZengMDPI AGDiabetology2673-45402025-05-01664510.3390/diabetology6060045Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)Julia Fischer0Nina Judith Hos1Sophie Tritschler2Joel Schmitz-Peters3Raja Ganesan4Chiara Calabrese5Petra Schiller6Hannah Brunnert7Angela Nowag8Sandra Winter9Ruth Hanßen10Katja Römer11Nazifa Qurishi12Isabelle Suarèz13Norma Jung14Clara Lehmann15Georg Plum16Michael Faust17Pia Hartmann18Nirmal Robinson19Department I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, GermanyDepartment I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyPoliclinic for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, 50936 Cologne, GermanyCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, GermanyCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, GermanyInstitute for Medical Statistics and Computational Biology, Medical Faculty and University Hospital of Cologne, University of Cologne, 50923 Cologne, GermanyDepartment I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyDepartment I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyDepartment I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyPoliclinic for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, 50936 Cologne, GermanyGemeinschaftspraxis Gotenring, 50679 Cologne, GermanyGemeinschaftspraxis Gotenring, 50679 Cologne, GermanyDepartment I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyDepartment I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyDepartment I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, GermanyInstitute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50923 Cologne, GermanyPoliclinic for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, 50936 Cologne, GermanyGerman Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 38124 Cologne, GermanyCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, Germany<b>Aims and Background:</b> Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 (SIRT1) plays an important role in regulating cellular metabolism, including T2DM and aging. Furthermore, we have recently demonstrated that SIRT1 critically regulates inflammatory pathways and autophagy during infection. Thus, we aimed to investigate SIRT1 expression and its correlation with autophagy in peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic patients. <b>Methods:</b> Clinical characteristics of the study subjects were obtained. SIRT1 and autophagic markers such as p62 and LC3-I/II were determined using Western blot analysis followed by densitometric analysis. <b>Results:</b> We found that SIRT1 levels were decreased in PBMCs of diabetic patients in an age-dependent manner. Importantly, reduced SIRT1 expression correlated with reduced LC3-II/I ratios, indicating reduced autophagy. Reduced SIRT1 also corresponded to decreased autophagic adaptor protein Sequestome-1/p62. <b>Conclusions:</b> In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients.https://www.mdpi.com/2673-4540/6/6/45type 2 diabetes mellitusPBMCSirtuin1autophagy
spellingShingle Julia Fischer
Nina Judith Hos
Sophie Tritschler
Joel Schmitz-Peters
Raja Ganesan
Chiara Calabrese
Petra Schiller
Hannah Brunnert
Angela Nowag
Sandra Winter
Ruth Hanßen
Katja Römer
Nazifa Qurishi
Isabelle Suarèz
Norma Jung
Clara Lehmann
Georg Plum
Michael Faust
Pia Hartmann
Nirmal Robinson
Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
Diabetology
type 2 diabetes mellitus
PBMC
Sirtuin1
autophagy
title Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
title_full Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
title_fullStr Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
title_full_unstemmed Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
title_short Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
title_sort age dependent loss of sirtuin1 sirt1 correlates with reduced autophagy in type 2 diabetic patients t2dm
topic type 2 diabetes mellitus
PBMC
Sirtuin1
autophagy
url https://www.mdpi.com/2673-4540/6/6/45
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