We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Pfkfb3 is transcriptionally upregulated in diabetic mouse liver through proliferative signals.
- Authors
Duran, Joan; Obach, Merc; Navarro-Sabate, Aurea; Manzano, Anna; Gómez, Marta; Rosa, Jose L.; Ventura, Francesc; Perales, Jose C.; Bartrons, Ramon
- Abstract
The ubiquitous isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (uPFK-2), a product of the Pfkfb3 gene, plays a crucial role in the control of glycolytic flux. In this study, we demonstrate that Pfkfb3 gene expression is increased in streptozotocin-induced diabetic mouse liver. The Pfkfb3/-3566 promoter construct linked to the luciferase reporter gene was delivered to the liver via hydrodynamic gene transfer. This promoter was upregulated in streptozotocin-induced diabetic mouse liver compared with transfected healthy cohorts. In addition, increases were observed in Pfkfb3 mRNA and uPFK-2 protein levels, and intrahepatic fructose-2,6-bisphosphate concentration. During streptozotocin-induced diabetes, phosphorylation of both p38 mitogen-activated protein kinase and Akt was detected, together with the overexpression of the proliferative markers cyclin D and E2F. These findings indicate that uPFK-2 induction is coupled to enhanced hepatocyte proliferation in streptozotocin-induced diabetic mouse liver. Expression decreased when hepatocytes were treated with either rapamycin or LY 294002. This shows that uPFK-2 regulation is phosphoinositide 3-kinase–Akt–mammalian target of rapamycin dependent. These results indicate that fructose-2,6-bisphosphate is essential to the maintenance of the glycolytic flux necessary for providing energy and biosynthetic precursors to dividing cells.
- Subjects
PEOPLE with diabetes; IMMUNOSUPPRESSIVE agents; PHOSPHOFRUCTOKINASE 1; GENETIC transformation; PROTEIN kinases; MESSENGER RNA
- Publication
FEBS Journal, 2009, Vol 276, Issue 16, p4555
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2009.07161.x