| First Author | Päth G | Year | 2020 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 319 |
| Issue | 2 | Pages | E338-E344 |
| PubMed ID | 32574111 | Mgi Jnum | J:296840 |
| Mgi Id | MGI:6469132 | Doi | 10.1152/ajpendo.00088.2020 |
| Citation | Path G, et al. (2020) NUPR1 preserves insulin secretion of pancreatic beta-cells during inflammatory stress by multiple low-dose streptozotocin and high-fat diet. Am J Physiol Endocrinol Metab 319(2):E338-E344 |
| abstractText | Obesity is associated with dyslipidemia and subclinical inflammation that promotes metabolic disturbances including insulin resistance and pancreatic beta-cell dysfunction. The nuclear protein, transcriptional regulator 1 (NUPR1) responds to cellular stresses and features tissue protective properties. To characterize the role of NUPR1 in endocrine pancreatic islets during inflammatory stress, we generated transgenic mice with beta-cell-specific Nupr1 overexpression (betaNUPR1). Under normal conditions, betaNUPR1 mice did not differ from wild type (WT) littermates and display normal glucose homeostasis and beta-cell mass. For induction of inflammatory conditions, mice were treated with multiple low-dose streptozotocin (mld-STZ) and/or fed a high-fat diet (HFD). All treatments significantly worsened glycaemia in WT mice, while betaNUPR1 mice substantially preserved insulin secretion and glucose tolerance. HFD increased beta-cell mass in all animals, with betaNUPR1 mice tending to show higher values. The improved outcome of betaNUPR1 mice was accompanied by decreased NF-kappaB activation and lymphocyte infiltration in response to mld-STZ. In vitro, isolated betaNUPR1 islets preserved insulin secretion and content with insignificantly low apoptosis during culture stress and IL-1beta exposure. These findings suggest that NUPR1 plays a vital role in the protection of beta-cells from apoptosis, related degradation of insulin storages and subsequent secretion during inflammatory and obesity-related tissue stress. |
