| First Author | Cerrada-Gimenez M | Year | 2012 |
| Journal | Transgenic Res | Volume | 21 |
| Issue | 4 | Pages | 843-53 |
| PubMed ID | 22180015 | Mgi Jnum | J:186591 |
| Mgi Id | MGI:5432669 | Doi | 10.1007/s11248-011-9579-6 |
| Citation | Cerrada-Gimenez M, et al. (2012) Altered glucose-stimulated insulin secretion in a mouse line with activated polyamine catabolism. Transgenic Res 21(4):843-53 |
| abstractText | Ubiquitous activation of polyamine catabolism has been demonstrated to have protective effects in mice on fat accumulation and insulin sensitivity/glucose tolerance in, both, normal conditions and after a high fat diet. We have analyzed the endocrine pancreas functionality in four months-old male mice overexpressing the rate limiting enzyme in the polyamine catabolism, spermidine/spermine N (1)-acetyltransferase (SSAT). The pancreatic SSAT activity was 37-fold elevated in the transgenic mice, which reduced the total pancreatic and islet pools of spermidine (71%) and spermine (69%), and increased putrescine and N (1)-acetyl spermidine. Reduction in the islet ATP levels (65%) was accompanied with increased transcription of 5'-AMP-activated protein kinase (AMPK) (1.5-fold) and Foxa2 (2.7-fold), and reduced HNF4alpha (67%) and HNF1alpha (92%), insulin 1 (47%), insulin 2 (50%), and Glut2 (57%). Moreover, the SSAT transgenic mice also presented increased beta cell area, decreased insulin production, and altered glucose-stimulated insulin secretion. It has been hypothesized that the acute activation of the polyamine catabolism produces a futile cycle that greatly decreases the energy reserves of the cell. The lower energy status would activate the energy expenditure regulator, AMPK, which would consequently repress the PI3K/Akt pathway, and activate the transcription factor Foxa2. |
