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

Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose this study was to investigate impact T2D on pancreatic depot. Pancreatic pads from 17 partial pancreatectomized patients (PPP) were collected, preadipocytes isolated, and in vitro differentiated. Patients grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD), T2D. Transcriptome profiles adipocytes assessed by RNAseq. Insulin sensitivity estimated quantifying AKT phosphorylation Western blots. Lipogenic capacity with oil red O staining, lipolytic activity via fatty acid release. Secreted factors measured ELISA. Comparative transcriptome analysis indicates defective upregulation genes governing adipogenesis ( NR1H3), lipogenesis FASN, SCD, ELOVL6, FADS1), lipolysis LIPE) during differentiation cells T2D–PPP. In addition, ratio leptin/adiponectin mRNA higher than NGT–PPP. Preadipocytes NGT–PPP more insulin sensitive T2D–PPP regard phosphorylation. Triglyceride accumulation similar NGT adipocytes. Despite a high expression receptors NPR1 NPR2 adipocytes, stimulated ANP 1.74-fold only. This stimulation further increased PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole forskolin receptor independently 1.88-fold 1.48-fold, respectively, solely cells. conclusion, metabolic status persistently affects These alterations could aggravate development