title: Altered glucose-stimulated insulin secretion in a mouse line with activated polyamine catabolism.
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.
authors.affiliation: 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
authors.forename: M
authors.initials: M
authors.lastname: Cerrada-Gimenez
authors.forename: M
authors.initials: M
authors.lastname: Tusa
authors.forename: A
authors.initials: A
authors.lastname: Casellas
authors.forename: E
authors.initials: E
authors.lastname: Pirinen
authors.forename: M
authors.initials: M
authors.lastname: Moya
authors.forename: F
authors.initials: F
authors.lastname: Bosch
authors.forename: L
authors.initials: L
authors.lastname: Alhonen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000494:pharmacology; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D000099228:Diamine N-Acetyltransferase
chemical_list: D055372:AMP-Activated Protein Kinases; D000123:Acetyltransferases; D000255:Adenosine Triphosphate; D005947:Glucose; D051542:Hepatocyte Nuclear Factor 3-beta; D007328:Insulin; D011073:Polyamines; D000099228:Diamine N-Acetyltransferase; C496503:Foxa2 protein, mouse