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

作者：Cerrada Gimenez M^*; Tusa M; Casellas A; Pirinen E; Moya M; Bosch F; Alhonen L

来源：Transgenic Research, 2012, 21(4): 843-853.

DOI：10.1007/s11248-011-9579-6

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

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%26apos;-AMP-activated protein kinase (AMPK) (1.5-fold) and Foxa2 (2.7-fold), and reduced HNF4 alpha (67%) and HNF1 alpha (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.

• 出版日期2012-8