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

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  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1555 (Electronic) Linking ISSN: 01931849 NLM ISO Abbreviation: Am J Physiol Endocrinol Metab Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, MD. : American Physiological Society
    • Subject Terms:
      DNA-Binding Proteins/*physiology ; Diet, High-Fat/*adverse effects ; Inflammation/*physiopathology ; Insulin Secretion/*physiology ; Insulin-Secreting Cells/*physiology ; Neoplasm Proteins/*physiology ; Streptozocin/*administration & dosage; Animals ; Apoptosis/physiology ; Blood Glucose/analysis ; Cells, Cultured ; DNA-Binding Proteins/genetics ; Female ; Gene Expression ; Homeostasis ; Inflammation/etiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasm Proteins/genetics ; Sex Factors
    • 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 characterize 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 βNUPR1 mice tending to show higher values. The improved outcome of βNUPR1 mice was accompanied by decreased NF-κB activation and lymphocyte infiltration in response to mld-STZ. In vitro, isolated βNUPR1 islets preserved insulin secretion and content with insignificantly low apoptosis during culture stress and IL-1β exposure. These findings suggest that NUPR1 plays a vital role in the protection of β-cells from apoptosis, related degradation of insulin storages and subsequent secretion during inflammatory and obesity-related tissue stress.
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    • Contributed Indexing:
      Keywords: IL-1β; NF-κB; NUPR1; high-fat diet; insulin secretion
    • Accession Number:
      0 (Blood Glucose)
      0 (DNA-Binding Proteins)
      0 (Neoplasm Proteins)
      0 (Nupr1 protein, mouse)
      5W494URQ81 (Streptozocin)
    • Publication Date:
      Date Created: 20200624 Date Completed: 20201026 Latest Revision: 20210802
    • Publication Date:
      20231215
    • Accession Number:
      PMC7473916
    • Accession Number:
      10.1152/ajpendo.00088.2020
    • Accession Number:
      32574111