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Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes

Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-for...

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Autores principales: Siegel-Axel, Dorothea, Barroso Oquendo, Morgana, Gerst, Felicia, Fend, Falko, Wagner, Robert, Heni, Martin, Königsrainer, Alfred, Häring, Hans-Ulrich, Fritsche, Andreas, Schleicher, Erwin, Birkenfeld, Andreas L., Stefan, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342602/
https://www.ncbi.nlm.nih.gov/pubmed/37446346
http://dx.doi.org/10.3390/ijms241311169
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author Siegel-Axel, Dorothea
Barroso Oquendo, Morgana
Gerst, Felicia
Fend, Falko
Wagner, Robert
Heni, Martin
Königsrainer, Alfred
Häring, Hans-Ulrich
Fritsche, Andreas
Schleicher, Erwin
Birkenfeld, Andreas L.
Stefan, Norbert
author_facet Siegel-Axel, Dorothea
Barroso Oquendo, Morgana
Gerst, Felicia
Fend, Falko
Wagner, Robert
Heni, Martin
Königsrainer, Alfred
Häring, Hans-Ulrich
Fritsche, Andreas
Schleicher, Erwin
Birkenfeld, Andreas L.
Stefan, Norbert
author_sort Siegel-Axel, Dorothea
collection PubMed
description Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-β1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover.
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spelling pubmed-103426022023-07-14 Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes Siegel-Axel, Dorothea Barroso Oquendo, Morgana Gerst, Felicia Fend, Falko Wagner, Robert Heni, Martin Königsrainer, Alfred Häring, Hans-Ulrich Fritsche, Andreas Schleicher, Erwin Birkenfeld, Andreas L. Stefan, Norbert Int J Mol Sci Article Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-β1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover. MDPI 2023-07-06 /pmc/articles/PMC10342602/ /pubmed/37446346 http://dx.doi.org/10.3390/ijms241311169 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 Article
Siegel-Axel, Dorothea
Barroso Oquendo, Morgana
Gerst, Felicia
Fend, Falko
Wagner, Robert
Heni, Martin
Königsrainer, Alfred
Häring, Hans-Ulrich
Fritsche, Andreas
Schleicher, Erwin
Birkenfeld, Andreas L.
Stefan, Norbert
Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes
title Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes
title_full Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes
title_fullStr Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes
title_full_unstemmed Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes
title_short Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes
title_sort extracellular matrix expression in human pancreatic fat cells of patients with normal glucose regulation, prediabetes and type 2 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342602/
https://www.ncbi.nlm.nih.gov/pubmed/37446346
http://dx.doi.org/10.3390/ijms241311169
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