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Transgenic Res. 2012 Aug;21(4):843-53. doi: 10.1007/s11248-011-9579-6. Epub 2011 Dec 18.

Altered glucose-stimulated insulin secretion in a mouse line with activated polyamine catabolism.

Author information

1
Biotechnology and Molecular Medicine, A.I. Virtanen Institute, Biocenter Kuopio, University of Eastern Finland, Kuopio Campus, P.O.Box 1627, 70211 Kuopio, Finland. Marc.CerradaGimenez@uef.fi

Abstract

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 N¹-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 N¹-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 HNF4α (67%) and HNF1α (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.

PMID:
22180015
DOI:
10.1007/s11248-011-9579-6
[Indexed for MEDLINE]

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