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

M. Cerrada-Gimenez, M. Tusa, A. Casellas, E. Pirinen, M. Moya, F. Bosch, L. Alhonen

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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. © 2011 Springer Science+Business Media B.V.
Original languageEnglish
Pages (from-to)843-853
JournalTransgenic Research
Volume21
Issue number4
DOIs
Publication statusPublished - 1 Aug 2012

Keywords

  • AMPK
  • ATP
  • Beta cells
  • Foxa2
  • Polyamines catabolism

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