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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/11169 |
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| author | Dorothea Siegel-Axel Morgana Barroso Oquendo Felicia Gerst Falko Fend Robert Wagner Martin Heni Alfred Königsrainer Hans-Ulrich Häring Andreas Fritsche Erwin Schleicher Andreas L. Birkenfeld Norbert Stefan |
| author_facet | Dorothea Siegel-Axel Morgana Barroso Oquendo Felicia Gerst Falko Fend Robert Wagner Martin Heni Alfred Königsrainer Hans-Ulrich Häring Andreas Fritsche Erwin Schleicher Andreas L. Birkenfeld Norbert Stefan |
| author_sort | Dorothea Siegel-Axel |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T01:38:22Z |
| format | Article |
| id | doaj.art-b2421575e2654d0f9ed3902695f840a8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:38:22Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b2421575e2654d0f9ed3902695f840a82023-11-18T16:49:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124131116910.3390/ijms241311169Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 DiabetesDorothea Siegel-Axel0Morgana Barroso Oquendo1Felicia Gerst2Falko Fend3Robert Wagner4Martin Heni5Alfred Königsrainer6Hans-Ulrich Häring7Andreas Fritsche8Erwin Schleicher9Andreas L. Birkenfeld10Norbert Stefan11Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyDepartment of General Pathology and Pathological Anatomy, University Hospital Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyDepartment of General, Visceral and Transplant Surgery, University Hospital Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyInstitute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, GermanyPreviously, 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.https://www.mdpi.com/1422-0067/24/13/11169(pre)adipocytesisletsfetuin-Amonocytesextracellular matrixadipose tissue |
| spellingShingle | Dorothea Siegel-Axel Morgana Barroso Oquendo Felicia Gerst Falko Fend Robert Wagner Martin Heni Alfred Königsrainer Hans-Ulrich Häring Andreas Fritsche Erwin Schleicher Andreas L. Birkenfeld Norbert Stefan Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes International Journal of Molecular Sciences (pre)adipocytes islets fetuin-A monocytes extracellular matrix adipose tissue |
| 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 | (pre)adipocytes islets fetuin-A monocytes extracellular matrix adipose tissue |
| url | https://www.mdpi.com/1422-0067/24/13/11169 |
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