Lajoie Claude, Béliveau Louise, Trudeau François, Lavoie Nathalie, Massicotte Guy, Gagnon Sylvain, Calderone Angelino
Department of Human Kinetics, Laurentian University, Ramsey Lake Road, ON P3E 2C6, Canada.
Can J Physiol Pharmacol. 2006 Nov;84(11):1205-13. doi: 10.1139/y06-070.
The present study tested the hypothesis that the phosphorylation and regulation of metabolic proteins implicated in glucose homeostasis were impaired in the heart of the type 2 diabetic Zucker-diabetic-fatty (ZDF) rat model. The onset of hyperglycaemia in ZDF rats was not uniform, instead it either progressed rapidly (3-4 weeks) or was delayed (6-8 weeks). In both the early and late onset hyperglycaemic ZDF rats, AMPKalpha Thr172 phosphorylation in the heart was significantly decreased. In the early onset hyperglycaemic ZDF rats, PKB Ser473 phosphorylation was reduced, whereas Thr308 phosphorylation was significantly increased. In the late onset hyperglycaemic ZDF rats, PKB Ser473 phosphorylation was unchanged, but Thr308 phosphorylation remained elevated. Cardiac GLUT4 protein and mRNA expression were significantly reduced in the early onset hyperglycaemic ZDF rats, whereas increased protein expression was observed in the late onset hyperglycaemic ZDF rats. In conclusion, the present study has demonstrated that following a more rapid onset of hyperglycaemia, the type 2 diabetic heart is more prone to alterations in the signaling proteins implicated in glucose metabolism.
本研究验证了一个假设，即在2型糖尿病Zucker糖尿病脂肪（ZDF）大鼠模型的心脏中，参与葡萄糖稳态的代谢蛋白的磷酸化和调节受到损害。ZDF大鼠高血糖的发作并不一致，而是要么迅速进展（3 - 4周），要么延迟（6 - 8周）。在早期和晚期发作的高血糖ZDF大鼠中，心脏中AMPKα Thr172磷酸化均显著降低。在早期发作的高血糖ZDF大鼠中，PKB Ser473磷酸化降低，而Thr308磷酸化显著增加。在晚期发作的高血糖ZDF大鼠中，PKB Ser473磷酸化未改变，但Thr308磷酸化仍升高。早期发作的高血糖ZDF大鼠心脏中GLUT4蛋白和mRNA表达显著降低，而晚期发作的高血糖ZDF大鼠中观察到蛋白表达增加。总之，本研究表明，在高血糖发作更快的情况下，2型糖尿病心脏更容易出现参与葡萄糖代谢的信号蛋白的改变。
