2型糖尿病（T2DM）是一种常见的代谢性疾病，由于其众多并发症，对健康造成重大风险。然而，黑色素对糖尿病小鼠的氧化应激、高血糖和抑郁的影响尚未得到广泛研究。我们的研究采用酶法从乌贼墨汁中提取黑色素，并利用光谱技术对其进行表征。值得注意的是，用碱性中性风味蛋白酶（ANF）提取的黑色素表现出优异的α-葡萄糖苷酶和α-淀粉酶抑制活性，同时增强肝癌细胞系（HepG2）胰岛素抵抗模型中的葡萄糖利用和肝糖原合成。进一步在T2DM ICR小鼠模型中评估ANF，显示其在缓解高血糖、降低糖基化血清蛋白水平、改善葡萄糖耐量以及调节总胆固醇（TC）、低密度脂蛋白（LDL）水平以及抗氧化指标（SOD、GSH-Px和MDA）方面具有显著的潜力，剂量为0.04 g·kg-1。此外，ANF在抗抑郁行为实验中对能量水平产生了积极影响，减少了不动时间。此外，ANF还积极影响肾细胞的密度和浸润状态，同时减轻了肝细胞的炎症增大和形态变化，在小鼠中未引起任何不良反应。总体而言，这些发现强调了ANF在治疗T2DM及其相关并发症方面的重要治疗潜力。通过增强脂质和葡萄糖代谢，减轻氧化应激和缓解抑郁症状，ANF成为多方位干预的有希望的候选药物。本文受版权保护。保留所有权利。

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that poses significant health risks due to its numerous complications. However, the effects of eumelanin on oxidative stress, hyperglycemia, and depression in diabetic mice haven't been extensively studied.Our study employed an enzymatic approach to extract eumelanin from squid ink and characterized it using spectroscopic techniques. Remarkably, eumelanin extracted with alkaline-neutral-flavor protease (ANF) displayed superior inhibitory activity against α-glucosidase and α-amylase, while enhancing glucose utilization and hepatic glycogen synthesis in human hepatocellular carcinoma cell line (HepG2) insulin resistance model. Further evaluation of ANF in a T2DM ICR mouse model demonstrated its significant potential in alleviating hyperglycemia, reducing glycosylated serum protein levels, improving glucose tolerance, and modulating total cholesterol (TC), low-density lipoprotein (LDL) levels, as well as antioxidant indices (SOD, GSH-Px, and MDA) at a dosage of 0.04 g·kg-1 . Additionally, ANF exhibited positive effects on energy levels and reduced immobility time in antidepressant behavioral experiments. Moreover, ANF positively influenced the density and infiltration state of renal cells, while mitigating inflammatory enlargement and deformation of liver cells, without inducing any adverse effects in mice.Overall, these findings underscore the significant therapeutic potential of ANF in the treatment of T2DM and its associated complications. By augmenting lipid and glucose metabolism, mitigating oxidative stress, and alleviating depression, ANF emerges as a promising candidate for multifaceted intervention. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.