Insulin-induced hypoglycaemia is co-ordinately regulated by liver and muscle during acute and chronic insulin stimulation in rainbow trout (Oncorhynchus mykiss)

Abstract

SUMMARYThe relative glucose intolerance of carnivorous fish species is often proposed to be a result of poor peripheral insulin action or possibly insulin resistance. In the present study, data from aortic cannulated rainbow trout receiving bovine insulin (75 mIU kg -1 ) injections show for the first time their ability to clear glucose in a very efficient manner. In another set of experiments, mRNA transcripts and protein phosphorylation status of proteins controlling glycaemia and glucose-related metabolism were studied during both acute and chronic treatment with bovine insulin. Our results show that fasted rainbow trout are well adapted at the molecular level to respond to increases in circulating insulin levels, and that this hormone is able to potentially improve glucose distribution and uptake by peripheral tissues. After acute insulin administration we found that to counter-regulate the insulininduced hypoglycaemia, trout metabolism is strongly modified. This short-term, efficient response to hypoglycaemia includes a rapid, coordinated response involving the reorganization of muscle and liver metabolism. During chronic insulin treatment some of the functions traditionally attributed to insulin actions in mammals were observed, including increased mRNA levels of glucose transporters and glycogen storage (primarily in the muscle) as well as decreased mRNA levels of enzymes involved in de novo glucose production (in the liver). Finally, we show that the rainbow trout demonstrates most of the classic metabolic adjustments employed by mammals to efficiently utilize glucose in the appropriate insulin context.

High levels of dietary fat impair glucose homeostasis in rainbow trout

“…Despite this reduced activity of glucose phosphorylating enzymes in the liver of trout fed the HFD, hepatic glycogen levels increased, favouring the idea that the storage of excess glucose as hepatic glycogen does not actually contribute to the control of glycaemia but simply reflects the glycaemic profile. This concept is not new in trout and has been observed recently in insulin-induced hypoglycaemic fish (Polakof et al, 2010). In both muscle and WAT, where gluconeogenesis plays a minor role, the inhibition of HK by the HFD was accompanied by depleted glycogen levels.…”

“…Insulin receptor substrate 1 (IRS1) and Akt protein level was assessed in the skeletal muscle, the main insulin-sensitive tissue. Anti-phosphoAkt Ser473 (Polakof et al, 2010), anti--tubulin (Polakof et al, 2010) and anti-IRS1 (Seiliez et al, 2011) have been shown to successfully cross-react with rainbow trout Akt, -tubulin and IRS1 protein, respectively.…”

“…The reduced number of insulin receptors in muscle and the low affinity of glucose transporter proteins for glucose are also proposed as possible causes of the low carbohydrate use in fish (Gutiérrez et al, 2006;Moon, 2001;Navarro et al, 1999). However, fasted rainbow trout were recently demonstrated to show efficient use of exogenous glucose and insulin sensitivity (Polakof et al, 2010). This finding suggests that the poor utilisation of dietary carbohydrates and the persistent hyperglycaemia in this species stems from an interaction between the dietary components rather than from an intrinsically unregulated glucose homeostasis.…”

“…Additionally, long-term palmitate feeding has been reported to induce hyperinsulinaemia, hyperglycaemia and loss of insulin sensitivity in the omnivorous Indian perch (Anabas testudineus), classic symptoms of the development of insulin resistance in mammals (Barma et al, 2006), suggesting that the mechanisms mediating the control and possible disturbance of glucose homeostasis are beingdigestible carbohydrate (Fernández et al, 2007;Kaushik and OlivaTeles, 1985;Venou et al, 2003) content as non-protein energy sources in order to spare protein for growth and reduce nitrogen loss to the aquatic environment. The positive protein-sparing effects of increased dietary lipid and digestible carbohydrate are, however, often associated with adverse effects in terms of fat deposition (Company et al, 1999;Jobling et al, 1998) and with the development of IGT in fish (Bergot, 1979;Cheng et al, 2006;Hutchins et al, 1998;Polakof et al, 2010).…”

Nutritional regulation of glucokinase: a cross-species story

“…On the other hand, injection of insulin in rainbow trout surprisingly reduced the level of GK gene expression in contrast to mammals and birds, even though insulin has a clear hypoglycaemic mammalian-type effect (217,237,238) . These data were confirmed using micro-osmotic pumps with insulin; the chronic infusion of insulin reduced also the level of GK mRNA (237) . Using rainbow trout hepatocytes, the same antagonist results of glucose and insulin on GK gene expression have been also shown.…”