Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity
| العنوان: | Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity |
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| المؤلفون: | Estela Lorza-Gil, Jürgen Machann, Felicia Gerst, Martin Heni, Anja Moller, Morgana Barroso Oquendo, Dorothea Siegel-Axel, Hans-Ulrich Häring, Susanne Ullrich, Robert Wagner, Alfred Königsrainer, Falko Fend, Andreas L. Birkenfeld |
| المصدر: | Am. J. Physiol.-Cell Physiol. 320, C1000-C1012 (2021) |
| بيانات النشر: | American Physiological Society, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Anp (atrial Natriuretic Peptide), Adipogenesis, Lipolysis, Pancreatic Fat Cell, Type 2 Diabetes, endocrine system diseases, Physiology, Adipose tissue, 030209 endocrinology & metabolism, Type 2 diabetes, 03 medical and health sciences, Delta-5 Fatty Acid Desaturase, 0302 clinical medicine, Internal medicine, Adipocytes, Humans, Insulin, Medicine, Obesity, Phosphorylation, Pancreas, Visceral fat, Triglycerides, Aged, Aged, 80 and over, ANP - Atrial natriuretic peptide, business.industry, Lipogenesis, nutritional and metabolic diseases, Cell Differentiation, Cell Biology, Middle Aged, medicine.disease, 030104 developmental biology, Endocrinology, Adipose Tissue, Diabetes Mellitus, Type 2, Female, business |
| الوصف: | Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose of this study was to investigate the impact of T2D on the pancreatic fat depot. Pancreatic fat pads from 17 partial pancreatectomized patients (PPP) were collected, pancreatic preadipocytes isolated, and in vitro differentiated. Patients were grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD), and T2D. Transcriptome profiles of preadipocytes and adipocytes were assessed by RNAseq. Insulin sensitivity was estimated by quantifying AKT phosphorylation on Western blots. Lipogenic capacity was assessed with oil red O staining, lipolytic activity via fatty acid release. Secreted factors were measured using ELISA. Comparative transcriptome analysis of preadipocytes and adipocytes indicates defective upregulation of genes governing adipogenesis ( NR1H3), lipogenesis ( FASN, SCD, ELOVL6, and FADS1), and lipolysis ( LIPE) during differentiation of cells from T2D–PPP. In addition, the ratio of leptin/adiponectin mRNA was higher in T2D than in NGT–PPP. Preadipocytes and adipocytes of NGT–PPP were more insulin sensitive than T2D–PPP cells in regard to AKT phosphorylation. Triglyceride accumulation was similar in NGT and T2D adipocytes. Despite a high expression of the receptors NPR1 and NPR2 in NGT and T2D adipocytes, lipolysis was stimulated by ANP 1.74-fold in NGT cells only. This stimulation was further increased by the PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole and forskolin increased lipolysis receptor independently 1.88-fold and 1.48-fold, respectively, solely in NGT cells. In conclusion, the metabolic status persistently affects differentiation and lipolysis of pancreatic adipocytes. These alterations could aggravate the development of T2D. |
| وصف الملف: | application/pdf |
| تدمد: | 1522-1563 0363-6143 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac7f9f90a2aaf98c371683e3ed3ff765 https://doi.org/10.1152/ajpcell.00595.2020 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ac7f9f90a2aaf98c371683e3ed3ff765 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221563 03636143 |
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