Glucose-dependent insulin release from genetically engineered K cells.
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.
Cheung
A T
AT
Department of Medicine, University of Alberta, Edmonton, AB T6G 2S2, Canada.
Dayanandan
B
B
Lewis
J T
JT
Korbutt
G S
GS
Rajotte
R V
RV
Bryer-Ash
M
M
Boylan
M O
MO
Wolfe
M M
MM
Kieffer
T J
TJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D019858:Enteroendocrine Cells / Q000166:cytology* / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011384:Proinsulin / Q000235:genetics; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013311:Streptozocin; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D007328:Insulin; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; D013311:Streptozocin; C013737:preproinsulin; D011384:Proinsulin; D005947:Glucose