Homocysteine (Hcy) is a sulfur-containing amino acid. An elevated level of Hcy is a risk factor for diabetes development. However, the mechanism of its effect on pancreatic β-cell function is unclear. In this study, we constructed a hyperhomocysteinemia (HHcy) mouse model by feeding mice a high methionine diet (HMD). The mice suffered impaired glucose tolerance and reduced insulin secretion. Furthermore, at the cellular level, INS1 cells exhibited impaired insulin secretory function after the Hcy intervention. Transcriptomics revealed that expression was downregulated and the downstream gene was upregulated in HHcy-induced mice compared with mice fed with normal diet. Insulin secretion could be restored by overexpression or fructose 1,6-bisphosphatase (FBPase) activity inhibition in INS1 cells. In conclusion, our study suggested that Hcy inhibited the insulin secretory function of pancreatic β-cells by suppressing expression, leading to the development of diabetes. may be a key target in the development of diabetes associated with elevated Hcy levels.

中文翻译：

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过量同型半胱氨酸通过抑制 Zbtb20 表达来抑制胰腺 β 细胞分泌功能

同型半胱氨酸（Hcy）是一种含硫氨基酸。 Hcy 水平升高是糖尿病发生的危险因素。然而，其影响胰腺β细胞功能的机制尚不清楚。在这项研究中，我们通过给小鼠喂食高蛋氨酸饮食（HMD）构建了高同型半胱氨酸血症（HHcy）小鼠模型。小鼠的葡萄糖耐量受损，胰岛素分泌减少。此外，在细胞水平上，INS1细胞在Hcy干预后表现出胰岛素分泌功能受损。转录组学显示，与正常饮食喂养的小鼠相比，HHcy 诱导的小鼠的表达下调，下游基因上调。 INS1 细胞中过度表达或果糖 1,6-二磷酸酶 (FBPase) 活性抑制可以恢复胰岛素分泌。总之，我们的研究表明，Hcy 通过抑制表达来抑制胰腺 β 细胞的胰岛素分泌功能，从而导致糖尿病的发生。可能是与 Hcy 水平升高相关的糖尿病发展的关键目标。