期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 297, 期 6, 页码 R1769-R1776出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00369.2009
关键词
fish; insulin; glucose metabolism; liver; muscle; metformin
类别
资金
- Agence Nationale de la Recherche [ANR-08-JCJC-0025-01]
- French National Institute for Agricultural Research
- Animal Physiology and Livestock Systems Division
- Xunta de Galicia
- Agence Nationale de la Recherche (ANR) [ANR-08-JCJC-0025] Funding Source: Agence Nationale de la Recherche (ANR)
Polakof S, Skiba-Cassy S, Panserat S. Glucose homeostasis is impaired by a paradoxical interaction between metformin and insulin in carnivorous rainbow trout. Am J Physiol Regul Integr Comp Physiol 297: R1769-R1776, 2009. First published September 30, 2009; doi:10.1152/ajpregu.00369.2009.-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.
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