Unexpected effect of insulin on glucose disposal explains glucose intolerance of rainbow trout

The physiological reasons why salmonids show glucose intolerance are unclear. In mammals, rapid clearance of a glucose load is mainly achieved through insulin-mediated inhibition of hepatic glucose production ( R_a) and stimulation of glucose disposal ( R_d), but the effects of insulin on R_a and R_d glucose have never been measured in fish. The goal of this study was to characterize the impact of insulin on the glucose kinetics of rainbow trout in vivo. Glucose fluxes were measured by continuous infusion of [6-³H]glucose before and during 4 h of insulin administration. The phosphorylated form of the key signaling proteins Akt and S6 in the insulin cascade were also examined, confirming activation of this pathway in muscle but not liver. Results show that insulin inhibits trout R_d glucose from 8.6 ± 0.6 to 5.4 ± 0.5 µmol kg^-1 min^-1: the opposite effect than classically seen in mammals. Such a different response may be explained by the contrasting effects of insulin on gluco/hexokinases of trout versus mammals. Insulin also reduced trout R_a from 8.5 ± 0.7 to 4.8 ± 0.6 µmol·kg^-1·min^-1, whereas it can almost completely suppresses R_a in mammals. The partial inhibition of R_a glucose may be because insulin only affects gluconeogenesis but not glycogen breakdown in trout. The small mismatch between the responses to insulin for R_d (-37%) and R_a glucose (-43%) gives trout a very limited capacity to decrease glycemia. We conclude that the glucose intolerance of rainbow trout can be explained by the inhibiting effect of insulin on glucose disposal.