Impaired PTPRD expression blunts insulin signalling via the unfolded protein response. (IMAGE)

First Hospital of Jilin University

Impaired PTPRD expression blunts insulin signalling via the unfolded protein response.

Caption

(a) Silencing of PTPRD in PHH leads to a significantly impaired (U-test) AKT phosphorylation (S473) following insulin stimulation, as assessed by western blot analysis (n=4). (b) Identification of 30 upregulated and 29 downregulated genes (false discovery rate (FDR) <0.05, Wald test) in liver samples from Ptprd+/− mice (n=3) compared with Ptprd+/+ mice (n=3) by RNA-seq. (c) Human homologs of the differentially expressed genes identified in the Ptprd+/− mice were correlated with PTPRD expression in liver samples from healthy individuals (n=38, GSE61260, Spearman’s correlation). (d) Correlation of PTPRD-associated genes (MANF, SDF2L1, HSPA5, DNAJB11 and ACACB) with transcriptional programmes implicated in diabetes development and insulin signalling (n=38, GSE61260, Spearman’s correlation). (e) Ranking of patients with obesity according to hepatic PTPRD expression into high-expressing (n=147, grey) and low-expressing (n=147, green) groups. Liver transcriptomic data obtained from GSE130991. (f) Analysis of clinical data from patients with obesity ranked according to PTPRD expression shows a significant association (T-test) between low hepatic PTPRD expression and increased fasting blood glucose, HbA1c, HOMA2 IR score, blood triglycerides and waist circumference. (g) Patients with low PTPRD expression display a significant (T-test) upregulation of MANF and SDF2L1 and a downregulation of ACACB, as compared with patients with high PTPRD expression. ACACB, acetyl-CoA carboxylase beta; AKT, AKT serine/threonine kinase; DNAJB11, dnaJ heat shock protein family (Hsp40) member B11; HbA1c, haemoglobin A1c; HOMA2, homeostasis model assessment 2; HSPA5, heat shock protein family A (Hsp70) Member 5; IR, insulin resistance; MANF, mesencephalic astrocyte-derived neurotrophic factor; PHH, primary human hepatocytes; PTPRD, protein tyrosine phosphatase delta; SDF2L1, stromal cell derived factor 2 like 1. *P<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

Credit

By Armando Andres Roca Suarez, Frank Jühling, Julien Moehlin et al.

Usage Restrictions

Credit must be given to the creator. Only noncommercial uses of the work are permitted.

License

CC BY-NC

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.