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Barroso Oquendo, M.* ; Siegel-Axel, D.I.* ; Gerst, F. ; Lorza-Gil, E. ; Moller, A. ; Wagner, R. ; Machann, J. ; Fend, F.* ; Königsrainer, A.* ; Heni, M. ; Häring, H.-U. ; Ullrich, S. ; Birkenfeld, A.L.

Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity.

Am. J. Physiol.-Cell Physiol. 320, C1000-C1012 (2021)
Postprint DOI PMC
Open Access Green
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, 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Anp (atrial Natriuretic Peptide) ; Adipogenesis ; Lipolysis ; Pancreatic Fat Cell ; Type 2 Diabetes; Adipose-tissue; Adipocyte; Leptin; Adiponectin; Phosphorylation; Homeostasis; Activation; Expression; Pathways; Women
ISSN (print) / ISBN 0363-6143
e-ISSN 1522-1563
Journal American Journal of Physiology - Cell Physiology
Quellenangaben Volume: 320, Issue: 6, Pages: C1000-C1012 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place 9650 Rockville Pike, Bethesda, Md 20814 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Grants state of Baden-Wurttemberg
Federal Ministry of Education and Research (BMBF)