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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.
- Source :
-
Nutrients [Nutrients] 2022 Sep 18; Vol. 14 (18). Date of Electronic Publication: 2022 Sep 18. - Publication Year :
- 2022
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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.
- Subjects :
- Animals
Blood Glucose metabolism
Cytokines metabolism
Diet, High-Fat
Glucose metabolism
Humans
Insulin
Mice
Neuro-Oncological Ventral Antigen
Obesity etiology
Obesity metabolism
RNA-Binding Proteins metabolism
Streptozocin
Bcl-2-Like Protein 11 metabolism
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Type 2 metabolism
Insulin-Secreting Cells metabolism
Subjects
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