These metabolic details take on particular importance as peripheral hyperinsulinemia and prediabetic stage are major risk factors for cognitive decline in aged individuals.
这些代谢细节特别重要，因为外周高胰岛素血症和糖尿病前期是老年人认知能力下降的主要危险因素
In addition to declining blood glucose homeostasis maintenance, the damage induced via elevated systemic insulin is multifaceted and affects multiple tissues, including the brain.
除了降低血糖维持稳态外，由全身胰岛素升高引起的损伤是多方面的，影响大脑在内的多个组织
While insulin is of short-term benefit to neurons, sustained systemic exposure can trigger neuronal insulin resistance (IR)11 and quadruple the risk of Alzheimer’s disease.
虽然胰岛素对神经元有短期益处，但持续全身暴露会引发胰岛素抵抗，并使阿尔兹海默症患病风险增加4倍。
Indeed, systemic hyperinsulinemia causes tissue ‘desensitization’ to insulin13, leading to IR that may develop well before the establishment of full diabetic syndromes13.
事实上，系统性高胰岛素血症会使组织对胰岛素脱敏，从而导致IR发生再糖尿病综合征之前
Peripheral insulin gains entry into the CNS through an active transport mechanism14,15 that can saturate cerebrospinal fluid (CSF) insulin levels at early prediabetic stages16.
外周胰岛素通过主动转运机制进入中枢神经系统，可在糖尿病前期使脑脊液胰岛素水平饱和
The resulting brain hyperinsulinemia, if persistent, is associated with cognitive decline and dementia6,8,17. Unfortunately, the pathways by which brain and CSF hyperinsulinemia exert their pathological effects on neurons remain poorly understood.
由此产生的脑高胰岛素症如果持续存在，可能与认知能力下降和痴呆有关。遗憾的是，大脑和脑脊液高胰岛素血症对神经元产生病理影响的途径仍知之甚少
