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This Article Full Text Full Text (PDF) All Versions of this Article: 297/6/R1769    most recent 00369.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Polakof, S. Articles by Panserat, S. PubMed PubMed Citation Articles by Polakof, S. Articles by Panserat, S.

Articles

Glucose homeostasis is impaired by a paradoxical interaction between metformin and insulin in carnivorous rainbow trout

¹Institut National de la Recherche Agronomique, UMR 1067 Nutrition Aquaculture et Génomique, Saint-Pée-sur-Nivelle, France; ²French Research Institute for Exploitation of the Sea, UMR 1067 Nutrition Aquaculture et Génomique, Plouzané, France; ³Université Bordeaux 1, UMR 1067 Nutrition Aquaculture et Génomique, Talence, France; and ⁴Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, Vigo, Spain

Submitted June 30, 2009 ; accepted in final form September 30, 2009

Utilizing rainbow trout (Oncorhynchus mykiss) as a known model of a "glucose-intolerant" and poor dietary glucose user, we assessed glucose utilization in fish chronically receiving two molecules able to improve glucose homeostasis: insulin and metformin. Our objectives were to assess the ability of rainbow trout to deal with a glucose load and to improve glucose utilization in fish receiving a chronic administration of insulin plus metformin treatments. Fish received (implanted miniosmotic pumps) saline, insulin, metformin, and insulin plus metformin solution for 4 days and then were subjected to a glucose challenge (intraperitoneal injection) to study glucose homeostasis, analyzing plasma glycemia, mRNA levels of glucose metabolism-related proteins, insulin signaling, and glycogen levels in liver and muscle. Control fish received a saline pump implantation and saline intraperitoneal injection. We found no evidence that the "glucose intolerance" in this species could be linked to any of the molecular markers of metabolism in the tissues analyzed. By contrast, very interestingly, we show for the first time, that metformin is not only unable to improve glucose homeostasis in trout, but, in fact, its counteracts the effects of insulin, creating an "insulin resistance," especially in the muscle. These results make trout an attractive original model to study both insulin and metformin effect on biological systems.

fish; insulin; glucose metabolism; liver; muscle; metformin