Department of Biology, University of Ottawa , Ottawa, Ontario , Canada.
Am J Physiol Regul Integr Comp Physiol. 2019 Apr 1;316(4):R387-R394. doi: 10.1152/ajpregu.00344.2018. Epub 2019 Jan 30.
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) and stimulation of glucose disposal ( R), but the effects of insulin on R and R 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-H]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 glucose from 8.6 ± 0.6 to 5.4 ± 0.5 µmol kg min: 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 from 8.5 ± 0.7 to 4.8 ± 0.6 µmol·kg·min, whereas it can almost completely suppresses R in mammals. The partial inhibition of R glucose may be because insulin only affects gluconeogenesis but not glycogen breakdown in trout. The small mismatch between the responses to insulin for R (-37%) and R 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.
鲑鱼类表现出葡萄糖不耐受的生理原因尚不清楚。在哺乳动物中，快速清除葡萄糖负荷主要通过胰岛素介导的抑制肝葡萄糖生成（R）和刺激葡萄糖摄取（R）来实现，但胰岛素对鱼类的 R 和 R 葡萄糖的作用从未被测量过。本研究的目的是描述胰岛素对虹鳟体内葡萄糖动力学的影响。在胰岛素给药前和 4 小时期间通过连续输注 [6-H]葡萄糖来测量葡萄糖通量。还检查了胰岛素级联中的关键信号蛋白 Akt 和 S6 的磷酸化形式，证实了该途径在肌肉中而不是在肝脏中被激活。结果表明，胰岛素抑制虹鳟 R 葡萄糖从 8.6±0.6 到 5.4±0.5 µmol kg min：与哺乳动物中经典的作用相反。这种不同的反应可能是由于胰岛素对虹鳟和哺乳动物的葡糖/己糖激酶的对比作用。胰岛素还将虹鳟 R 从 8.5±0.7 降低到 4.8±0.6 µmol·kg·min，而在哺乳动物中几乎可以完全抑制 R。R 葡萄糖的部分抑制可能是因为胰岛素仅影响糖异生而不影响虹鳟的糖原分解。R 和 R 葡萄糖对胰岛素反应之间的小差异（-37%和-43%）使虹鳟降低血糖的能力非常有限。我们得出结论，虹鳟葡萄糖不耐受可以用胰岛素对葡萄糖摄取的抑制作用来解释。
