NUPR1 preserves insulin secretion of pancreatic ß-cells during inflammatory stress by multiple low-dose streptozotocin and high-fat diet.
Am J Physiol Endocrinol Metab
; 319(2): E338-E344, 2020 08 01.
Article
in En
| MEDLINE
| ID: mdl-32574111
ABSTRACT
Obesity is associated with dyslipidemia and subclinical inflammation that promotes metabolic disturbances including insulin resistance and pancreatic ß-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 ß-cell-specific Nupr1 overexpression (ßNUPR1). Under normal conditions, ßNUPR1 mice did not differ from wild type (WT) littermates and display normal glucose homeostasis and ß-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 ßNUPR1 mice substantially preserved insulin secretion and glucose tolerance. HFD increased ß-cell mass in all animals, with ßNUPR1 mice tending to show higher values. The improved outcome of ßNUPR1 mice was accompanied by decreased NF-κB activation and lymphocyte infiltration in response to mld-STZ. In vitro, isolated ßNUPR1 islets preserved insulin secretion and content with insignificantly low apoptosis during culture stress and IL-1ß exposure. These findings suggest that NUPR1 plays a vital role in the protection of ß-cells from apoptosis, related degradation of insulin storages and subsequent secretion during inflammatory and obesity-related tissue stress.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Streptozocin
/
DNA-Binding Proteins
/
Insulin-Secreting Cells
/
Diet, High-Fat
/
Insulin Secretion
/
Inflammation
/
Neoplasm Proteins
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Am J Physiol Endocrinol Metab
Journal subject:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Year:
2020
Type:
Article
Affiliation country:
Germany