Abstract
Genetic engineering of non-beta cells to release insulin upon feeding could be a therapeutic modality for patients with diabetes. A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP). Mice expressing this transgene produced human insulin specifically in gut K cells. This insulin protected the mice from developing diabetes and maintained glucose tolerance after destruction of the native insulin-producing beta cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Glucose / metabolism
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Cell Line
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Cloning, Molecular
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / therapy*
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Enteroendocrine Cells / cytology*
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Enteroendocrine Cells / metabolism*
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Gastric Inhibitory Polypeptide / biosynthesis
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Gastric Inhibitory Polypeptide / genetics
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Gene Expression
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Genetic Engineering
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Genetic Therapy*
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Glucose / administration & dosage
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Glucose / metabolism*
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Glucose Tolerance Test
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Humans
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Insulin / biosynthesis
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Insulin / genetics
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Insulin / metabolism*
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Mice
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Mice, Transgenic
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Proinsulin / genetics
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Promoter Regions, Genetic
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Protein Precursors / genetics
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Stem Cells / cytology
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Stem Cells / metabolism
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Streptozocin
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Transfection
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Transgenes
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Tumor Cells, Cultured
Substances
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Blood Glucose
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Insulin
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Protein Precursors
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Gastric Inhibitory Polypeptide
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Streptozocin
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preproinsulin
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Proinsulin
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Glucose