Glucose homeostasis is impaired by a paradoxical interaction between metformin and insulin in carnivorous rainbow trout.
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.
Polakof
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Institut National de la Recherche Agronomique, UMR 1067 Nutrition Aquaculture et Génomique, Saint-Pée-sur-Nivelle, France. spolakof@uvigo.es
Skiba-Cassy
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Panserat
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D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D005247:Feeding Behavior; D005786:Gene Expression Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000008:administration & dosage; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D006706:Homeostasis; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D007004:Hypoglycemic Agents; D007328:Insulin; D008112:Liver Glycogen; D012333:RNA, Messenger; D008687:Metformin; D005947:Glucose