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Am J Physiol Regul Integr Comp Physiol 297: R707-R715, 2009. First published June 24, 2009; doi:10.1152/ajpregu.00120.2009
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ARTICLES

Metformin improves postprandial glucose homeostasis in rainbow trout fed dietary carbohydrates: a link with the induction of hepatic lipogenic capacities?

S. Panserat,1,2,3 S. Skiba-Cassy,1,2,3 I. Seiliez,1,2,3 M. Lansard,1,2,3 E. Plagnes-Juan,1,2,3 C. Vachot,1,2,3 P. Aguirre,1,2,3 L. Larroquet,1,2,3 G. Chavernac,4 F. Medale,1,2,3 G. Corraze,1,2,3 S. Kaushik,1,2,3 and T. W. Moon5

1Institut National de la Recherche Agronomique, Joint Research Unit 1067 Nutrition Aquaculture et Génomique, Saint-Pée-sur-Nivelle; 2Institut Français de Recherche pour l'Exploitation de la Mer, Joint Research Unit 1067 Nutrition Aquaculture et Génomique, Plouzané; 3Université Bordeaux 1, Joint Research Unit 1067 Nutrition Aquaculture et Génomique, Talence; 4Department of Toxicology, Merck Santé, Lyon, France; and 5Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada

Submitted 23 February 2009 ; accepted in final form 17 June 2009

Carnivorous fish are poor users of dietary carbohydrates and are considered to be glucose intolerant. In this context, we have tested, for the first time in rainbow trout, metformin, a common anti-diabetic drug, known to modify muscle and liver metabolism and to control hyperglycemia in mammals. In the present study, juvenile trout were fed with very high levels of carbohydrates (30% of the diet) for this species during 10 days followed by feeding with pellets supplemented with metformin (0.25% of the diet) for three additional days. Dietary metformin led to a significant reduction in postprandial glycemia in trout, demonstrating unambiguously the hypoglycemic effect of this drug. No effect of metformin was detected on mRNA levels for glucose transporter type 4 (GLUT4), or enzymes involved in glycolysis, mitochondrial energy metabolism, or on glycogen level in the white muscle. Expected inhibition of hepatic gluconeogenic (glucose-6-phosphatase, fructose-1,6-bisphosphatase, and phosphoenolpyruvate carboxykinase) mRNA levels was not found, showing instead paradoxically higher mRNA levels for these genes after drug treatment. Finally, metformin treatment was associated with higher mRNA levels and activities for lipogenic enzymes (fatty acid synthase and glucose-6-phosphate dehydrogenase). Overall, this study strongly supports that the induction of hepatic lipogenesis by dietary glucose may permit a more efficient control of postprandial glycemia in carnivorous fish fed with high carbohydrate diets.

glucose; anti-diabetic drug; muscle; liver; carnivorous fish



Address for reprint requests and other correspondence: S. Panserat, INRA, UMR1067 Nutrition Aquaculture Génomique, Pôle d'hydrobiologie, CD918, F-64310 St-Pée-sur-Nivelle, France (e-mail: panserat{at}st-pee.inra.fr)




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S. Polakof, S. Skiba-Cassy, and S. Panserat
Glucose homeostasis is impaired by a paradoxical interaction between metformin and insulin in carnivorous rainbow trout
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2009; 297(6): R1769 - R1776.
[Abstract] [Full Text] [PDF]




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