Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes...

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.