Insulin regulation of hepatic gene expression in rainbow trout (Oncorhynchus mykiss)

Glucose intolerance and limited efficiency in dietary carbohydrates use are characteristic features of carnivorous fish. The absence of post-prandial down-regulation of gluconeogenic gene expressions in rainbow trout suggests an insulin resistance state as observed in human patients with non-insulin-dependent diabetes mellitus. In order to investigate the ability of insulin to control hepatic gene expression in rainbow trout, we performed intra-peritoneal injection of bovine insulin to 24 hours-fasted rainbow trout. We demonstrated that insulin was able in vivo to activate its signaling pathway as indicated by the activation of the protein kinase B and to modulate expression of several genes including glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, carnitine palmitoyltransferase 1 and PPAR gamma co-activator 1 alpha. These results demonstrated the intrinsic capacity of insulin to regulate gene expression in rainbow trout liver. Consequently, the absence of post-prandial regulation of hepatic gluconeogenesis in trout cannot be directly attributed to default in insulin signaling. Since amino acids have recently been proposed as potent down regulators of insulin signaling in mammals we hypothesize that the ability of insulin to control expression of metabolic genes could be disrupted in carnivorous fish by the high dietary protein levels. This hypothesis is under investigation. This work was supported by the French Aquitaine region.