海马胰岛素信号缺陷和tau蛋白磷酸化增加与肥胖和年龄诱导的外周胰岛素抵抗有关：对 Zucker 大鼠的研究。
Deficient hippocampal insulin signaling and augmented Tau phosphorylation is related to obesity- and age-induced peripheral insulin resistance: a study in Zucker rats.
作者信息
Špolcová Andrea, Mikulášková Barbora, Kršková Katarína, Gajdošechová Lucia, Zórad Štefan, Olszanecki Rafał, Suski Maciej, Bujak-Giżycka Beata, Železná Blanka, Maletínská Lenka
机构信息
Institute of Organic Chemistry and Biochemistry, Prague, 166 10, Czech Republic.
出版信息
BMC Neurosci. 2014 Sep 25;15:111. doi: 10.1186/1471-2202-15-111.
BACKGROUND
Insulin signaling and Tau protein phosphorylation in the hippocampi of young and old obese Zucker fa/fa rats and their lean controls were assessed to determine whether obesity-induced peripheral insulin resistance and aging are risk factors for central insulin resistance and whether central insulin resistance is related to the pathologic phosphorylation of the Tau protein.
RESULTS
Aging and obesity significantly attenuated the phosphorylation of the insulin cascade kinases Akt (protein kinase B, PKB) and GSK-3β (glycogen synthase kinase 3β) in the hippocampi of the fa/fa rats. Furthermore, the hyperphosphorylation of Tau Ser396 alone and both Tau Ser396 and Thr231 was significantly augmented by aging and obesity, respectively, in the hippocampi of these rats.
CONCLUSIONS
Both age-induced and obesity-induced peripheral insulin resistance are associated with central insulin resistance that is linked to hyperTau phosphorylation. Peripheral hyperinsulinemia, rather than hyperglycemia, appears to promote central insulin resistance and the Tau pathology in fa/fa rats.
背景
评估年轻和老年肥胖 Zucker fa/fa 大鼠及其瘦型对照的海马中胰岛素信号传导和 Tau 蛋白磷酸化，以确定肥胖诱导的外周胰岛素抵抗和衰老是否是中枢胰岛素抵抗的危险因素，以及中枢胰岛素抵抗是否与 Tau 蛋白的病理性磷酸化有关。
结果
衰老和肥胖显著减弱了 fa/fa 大鼠海马中胰岛素级联激酶 Akt（蛋白激酶 B，PKB）和 GSK-3β（糖原合酶激酶 3β）的磷酸化。此外，在这些大鼠的海马中，衰老和肥胖分别显著增加了单独的 Tau Ser396 以及 Tau Ser396 和 Thr231 的过度磷酸化。
结论
年龄诱导和肥胖诱导的外周胰岛素抵抗均与中枢胰岛素抵抗相关，而中枢胰岛素抵抗与 Tau 蛋白过度磷酸化有关。外周高胰岛素血症而非高血糖似乎促进了 fa/fa 大鼠的中枢胰岛素抵抗和 Tau 病理改变。
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