Physiology Research Center, Institute of Neuropharmacology and Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
Mol Neurobiol. 2023 Jun;60(6):3486-3495. doi: 10.1007/s12035-023-03285-z. Epub 2023 Mar 6.
Alzheimer's disease (AD) is closely related to type 2 diabetes (T2D). This study investigated the impact of high-intensity interval training (HIIT) on diabetes-induced disturbances in AD-related factors (including AMP-activated protein kinase (AMPK), glycogen synthase kinase-3β (GSK3β), and tau protein) in the hippocampus, with the main focus on adiponectin signaling.In total, 28 male Wistar rats at the age of 8 weeks were randomly assigned to four groups (n = 7 in each group): control (Con), type 2 diabetes (T2D), HIIT (Ex), and type 2 diabetes + HIIT (T2D + Ex). T2D was induced by a high-fat diet plus a single dose of streptozotocin (STZ). Rats in Ex and T2D + Ex groups performed 8 weeks of HIIT (running at 8-95% of V, 4-10 intervals). Insulin and adiponectin levels in serum and hippocampus were measured along with hippocampal expression of insulin and adiponectin receptors, phosphorylated AMPK, dephosphorylated GSK3β, and phosphorylated tau. Homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for insulin resistance beta (HOMA-β), and quantitative insulin sensitivity check index (QUICKI) were calculated to assess insulin resistance and sensitivity. T2D decreased insulin and adiponectin levels in serum and hippocampus, as well as the hippocampal levels of insulin and adiponectin receptors and AMPK, but increased GSK3β and tau in the hippocampus. HIIT reversed diabetes-induced impairments and consequently decreased tau accumulation in the hippocampus of diabetic rats. HOMA-IR, HOMA-β, and QUICKI were improved in Ex and T2D + Ex groups. Overall, our results confirmed that T2D has undesirable effects on the levels of some Alzheimer's-related factors in the hippocampus, and HIIT could ameliorate these impairments in the hippocampus.
阿尔茨海默病（AD）与 2 型糖尿病（T2D）密切相关。本研究探讨了高强度间歇训练（HIIT）对糖尿病引起的 AD 相关因素（包括 AMP 激活蛋白激酶（AMPK）、糖原合成酶激酶-3β（GSK3β）和 tau 蛋白）在海马体中变化的影响，主要关注脂联素信号。共有 28 只 8 周龄雄性 Wistar 大鼠被随机分为四组（每组 7 只）：对照组（Con）、2 型糖尿病组（T2D）、HIIT 组（Ex）和 2 型糖尿病+HIIT 组（T2D+Ex）。T2D 是通过高脂肪饮食加单次链脲佐菌素（STZ）诱导的。Ex 和 T2D+Ex 组大鼠进行 8 周的 HIIT（以 8-95%的 V、4-10 个间隔跑步）。测量血清和海马中胰岛素和脂联素水平，以及海马胰岛素和脂联素受体、磷酸化 AMPK、去磷酸化 GSK3β 和磷酸化 tau 的表达。计算稳态模型评估的胰岛素抵抗（HOMA-IR）、稳态模型评估的胰岛素抵抗β（HOMA-β）和定量胰岛素敏感性检查指数（QUICKI）来评估胰岛素抵抗和敏感性。T2D 降低了血清和海马中的胰岛素和脂联素水平，以及海马中的胰岛素和脂联素受体和 AMPK 水平，但增加了海马中的 GSK3β 和 tau。HIIT 逆转了糖尿病引起的损伤，从而减少了糖尿病大鼠海马中的 tau 积累。Ex 和 T2D+Ex 组的 HOMA-IR、HOMA-β 和 QUICKI 得到改善。总的来说，我们的结果证实，T2D 对海马中某些与阿尔茨海默病相关的因素水平有不良影响，而 HIIT 可以改善海马中的这些损伤。
