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

Content Provider	Springer Nature Link
Author	Cerrada Gimenez, M. Tusa, M. Casellas, A. Pirinen, E. Moya, M. Bosch, F. Alhonen, L.
Copyright Year	2011
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 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 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.
Starting Page	843
Ending Page	853
Page Count	11
File Format	PDF
ISSN	09628819
Journal	Transgenic Research
Volume Number	21
Issue Number	4
e-ISSN	15739368
Language	English
Publisher	Springer Netherlands
Publisher Date	2011-12-18
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	AMPK ATP Beta cells Foxa2 Polyamines catabolism Plant Genetics & Genomics Plant Sciences Animal Genetics and Genomics Molecular Medicine Human Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics Animal Science and Zoology Biotechnology Agronomy and Crop Science

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