NUPR1 preserves insulin secretion of pancreatic β-cells during inflammatory stress by multiple low dose streptozotocin and high fat diet.

NUPR1 preserves insulin secretion of pancreatic β-cells during inflammatory stress by multiple low dose streptozotocin and high fat diet. Am J Physiol Endocrinol Metab. 2020 Jun 23;: Authors: Päth G, Mehana AE, Pilz IH, Alt M, Baumann J, Sommerer I, Hoffmeister A, Seufert J Abstract Obesity is associated with dyslipidemia and subclinical inflammation that promotes metabolic disturbances including insulin resistance and pancreatic β-cell dysfunction. The nuclear protein, transcriptional regulator 1 (NUPR1) responds to cellular stresses and features tissue protective properties. To characterise the role of NUPR1 in endocrine pancreatic islets during inflammatory stress, we generated transgenic mice with β-cell-specific Nupr1 overexpression (βNUPR1). Under normal conditions, βNUPR1 mice did not differ from wild type (WT) littermates and display normal glucose homeostasis and β-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 βNUPR1 mice substantially preserved insulin secretion and glucose tolerance. HFD increased β-cell mass in all animals, with β-NUPR1 mice tending to show higher values. The improved outcome of βNUPR1 mice was accompanied by decreased NF-kB activation and lymphocyte infiltration in response to mld-STZ. In vitro, isolated βNUPR1 islets pres...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research