Insulin resistance in brain has been reported in Alzheimer's diseases (AD). Insulin signaling is important for homeostasis in brain function and reported to be disturbed in neurons leading to tau phosphorylation and neurofibrillary tangles. Many investigations of insulin in neurons have been reported; however, it has not been reported whether astrocytes also produce insulin. In the present study, we assessed the expression of insulin in astrocytes cultured from rat embryonic brain and the effects of amyloid β_1-42 (Aβ) and lipopolysaccharide (LPS) on the expression. We found that astrocytes expressed preproinsulin mRNAs and insulin protein, and that Aβ or LPS decreased these expressions. Antioxidants, glutathione and N-acetylcysteine, restored the decreases in insulin mRNA expression by Aβ and by LPS. Insulin protein was detected in astrocyte conditioned medium. These results suggest that astrocytes express and secrete insulin. Oxidative stress might be involved in the decreased insulin expression by Aβ or LPS. The insulin decrease by Aβ in astrocytes could be a novel disturbing mechanism for brain insulin signaling in AD.

在阿尔茨海默氏病（AD）中已经报道了大脑中的胰岛素抵抗。胰岛素信号传导对于脑功能的动态平衡很重要，据报道在神经元中胰岛素信号受到干扰，导致tau磷酸化和神经原纤维缠结。已经报道了许多神经元中胰岛素的研究。然而，尚未报道星形胶质细胞是否也产生胰岛素。在本研究中，我们评估了胰岛素在大鼠胚胎脑培养的星形胶质细胞中的表达以及淀粉样蛋白_1-1-4（Aβ）和脂多糖（LPS）对其表达的影响。我们发现星形胶质细胞表达胰岛素原前mRNA和胰岛素蛋白，而Aβ或LPS降低了这些表达。抗氧化剂，谷胱甘肽和氮-乙酰半胱氨酸通过Aβ和LPS恢复了胰岛素mRNA表达的下降。在星形胶质细胞条件培养基中检测到胰岛素蛋白。这些结果表明星形胶质细胞表达和分泌胰岛素。氧化应激可能与Aβ或LPS导致的胰岛素表达降低有关。星形胶质细胞中Aβ引起的胰岛素减少可能是AD中脑胰岛素信号传导的一种新的干扰机制。