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首页> 外国专利> Modified Nucleotide Sequence Encoding Glucagon-Like Peptide-1 (GLP-1), Nucleic Acid Construct Comprising Same for Production of Glucagon-Like Peptide-1 (GLP-1), Human Cells Comprising Said Construct and Insulin-Producing Constructs, and Method of Use Thereof

Modified Nucleotide Sequence Encoding Glucagon-Like Peptide-1 (GLP-1), Nucleic Acid Construct Comprising Same for Production of Glucagon-Like Peptide-1 (GLP-1), Human Cells Comprising Said Construct and Insulin-Producing Constructs, and Method of Use Thereof

机译：编码胰高血糖素样肽-1（GLP-1）的修饰的核苷酸序列，用于生产胰高血糖素样肽-1（GLP-1）的包含相同的核酸构建体，包含所述构建体和胰岛素生产构建体的人细胞及其制备方法使用它

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摘要

An isolated chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1 is provided. Also provided is an isolated modified chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1. Recombinant expression vectors comprising the chimeric GLP-1 nucleic acid sequences, which produce GLP-1 constitutively are provided, as are human cells transfected with such an expression vector in combination with an expression vector comprising a proinsulin nucleic acid sequence and an expression vector comprising a furin and a glucose-regulatable TGF-alpha promoter. Methods of producing human GLP-1 constitutively are provided as are method of producing GLP-1 and insulin or in a glucose-dependent manner using such transfected cells. Methods of treating a subject having Type II diabetes and methods of treating a subject prone to hyperglycemia or suffering from hyperglycemia are provided in which transfected cells produce human GLP-1 and insulin in a glucose-dependent manner. Also provided are methods of reducing weight in a subject by implanting into the subject transfected cells which produce human GLP-1 and insulin in a glucose-dependent manner.
机译：提供了分离的嵌合GLP-1核酸序列，其编码人胰岛素原前导序列，胰高血糖素样肽-1（GLP-1），以及人胰岛素原前导序列和GLP-1之间的弗林蛋白酶可切割位点。 。还提供了分离的修饰的嵌合GLP-1核酸序列，其编码人胰岛素原前导序列，胰高血糖素样肽-1（GLP-1），以及人胰岛素原前导序列和GLP之间的弗林蛋白酶可切割位点。 -1。提供了包含组成型产生GLP-1的嵌合GLP-1核酸序列的重组表达载体，以及用这种表达载体转染的人细胞与包含胰岛素原核酸序列的表达载体和包含β-内酰胺酶的表达载体的组合。弗林蛋白酶和葡萄糖可调节的TGF-α启动子。提供了组成型生产人GLP-1的方法，以及使用这种转染的细胞生产GLP-1和胰岛素的方法或以葡萄糖依赖性的方式。提供了治疗患有II型糖尿病的受试者的方法和治疗易于发生高血糖症或患有高血糖症的受试者的方法，其中转染的细胞以葡萄糖依赖性方式产生人GLP-1和胰岛素。还提供了通过将以葡萄糖依赖性方式产生人GLP-1和胰岛素的转染细胞植入受试者体内来减轻受试者体重的方法。

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