Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
Aims and Background: 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. T...
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| Published in | Diabetology Vol. 6; no. 6; p. 45 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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MDPI AG
23.05.2025
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| Abstract | Aims and Background: 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. Methods: 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. Results: 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. Conclusions: In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients. |
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| AbstractList | Aims and Background: 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. Methods: 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. Results: 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. Conclusions: In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients. |
| Author | Plum, Georg Winter, Sandra Qurishi, Nazifa Ganesan, Raja Hos, Nina Judith Faust, Michael Fischer, Julia Lehmann, Clara Nowag, Angela Hanßen, Ruth Jung, Norma Brunnert, Hannah Tritschler, Sophie Robinson, Nirmal Römer, Katja Schmitz-Peters, Joel Schiller, Petra Suarèz, Isabelle Hartmann, Pia Calabrese, Chiara |
| Author_xml | – sequence: 1 givenname: Julia orcidid: 0000-0001-6138-7454 surname: Fischer fullname: Fischer, Julia – sequence: 2 givenname: Nina Judith surname: Hos fullname: Hos, Nina Judith – sequence: 3 givenname: Sophie surname: Tritschler fullname: Tritschler, Sophie – sequence: 4 givenname: Joel surname: Schmitz-Peters fullname: Schmitz-Peters, Joel – sequence: 5 givenname: Raja surname: Ganesan fullname: Ganesan, Raja – sequence: 6 givenname: Chiara surname: Calabrese fullname: Calabrese, Chiara – sequence: 7 givenname: Petra surname: Schiller fullname: Schiller, Petra – sequence: 8 givenname: Hannah surname: Brunnert fullname: Brunnert, Hannah – sequence: 9 givenname: Angela surname: Nowag fullname: Nowag, Angela – sequence: 10 givenname: Sandra surname: Winter fullname: Winter, Sandra – sequence: 11 givenname: Ruth orcidid: 0000-0002-7283-9302 surname: Hanßen fullname: Hanßen, Ruth – sequence: 12 givenname: Katja surname: Römer fullname: Römer, Katja – sequence: 13 givenname: Nazifa surname: Qurishi fullname: Qurishi, Nazifa – sequence: 14 givenname: Isabelle orcidid: 0000-0002-9863-9675 surname: Suarèz fullname: Suarèz, Isabelle – sequence: 15 givenname: Norma surname: Jung fullname: Jung, Norma – sequence: 16 givenname: Clara surname: Lehmann fullname: Lehmann, Clara – sequence: 17 givenname: Georg surname: Plum fullname: Plum, Georg – sequence: 18 givenname: Michael surname: Faust fullname: Faust, Michael – sequence: 19 givenname: Pia surname: Hartmann fullname: Hartmann, Pia – sequence: 20 givenname: Nirmal orcidid: 0000-0002-7361-9491 surname: Robinson fullname: Robinson, Nirmal |
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