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Nova1 or Bim Deficiency in Pancreatic β-Cells Does Not Alter Multiple Low-Dose Streptozotocin-Induced Diabetes and Diet-Induced Obesity in Mice.

Authors :
Brahma MK
Xiao P
Popa M
Negueruela J
Vandenbempt V
Demine S
Cardozo AK
Gurzov EN
Source :
Nutrients [Nutrients] 2022 Sep 18; Vol. 14 (18). Date of Electronic Publication: 2022 Sep 18.
Publication Year :
2022

Abstract

The loss of functional pancreatic β-cell mass is an important hallmark of both type 1 and type 2 diabetes. The RNA-binding protein NOVA1 is expressed in human and rodent pancreatic β-cells. Previous in vitro studies indicated that NOVA1 is necessary for glucose-stimulated insulin secretion and its deficiency-enhanced cytokine-induced apoptosis. Moreover, Bim, a proapoptotic protein, is differentially spliced and potentiates apoptosis in NOVA1-deficient β-cells in culture. We generated two novel mouse models by Cre-Lox technology lacking Nova1 (βNova1 <superscript>-/-</superscript> ) or Bim (βBim <superscript>-/-</superscript> ) in β-cells. To test the impact of Nova1 or Bim deletion on β-cell function, mice were subjected to multiple low-dose streptozotocin (MLD-STZ)-induced diabetes or high-fat diet-induced insulin resistance. β-cell-specific Nova1 or Bim deficiency failed to affect diabetes development in response to MLD-STZ-induced β-cell dysfunction and death evidenced by unaltered blood glucose levels and pancreatic insulin content. In addition, body composition, glucose and insulin tolerance test, and pancreatic insulin content were indistinguishable between control and βNova1 <superscript>-/-</superscript> or βBim <superscript>-/-</superscript> mice on a high fat diet. Thus, Nova1 or Bim deletion in β-cells does not impact on glucose homeostasis or diabetes development in mice. Together, these data argue against an in vivo role for the Nova1-Bim axis in β-cells.

Details

Language :
English
ISSN :
2072-6643
Volume :
14
Issue :
18
Database :
MEDLINE
Journal :
Nutrients
Publication Type :
Academic Journal
Accession number :
36145242
Full Text :
https://doi.org/10.3390/nu14183866