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Science 8 December 2000:
Vol. 290. no. 5498, pp. 1959 - 1962
DOI: 10.1126/science.290.5498.1959
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Reports

Glucose-Dependent Insulin Release from Genetically Engineered K Cells

Anthony T. Cheung,13 Bama Dayanandan,1 Jamie T. Lewis,1 Gregory S. Korbutt,2 Ray V. Rajotte,2 Michael Bryer-Ash,4 Michael O. Boylan,5 M. Michael Wolfe,5 Timothy J. Kieffer13*

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.

1 Departments of Medicine and Physiology, and
2 Department of Surgery, University of Alberta, Edmonton, AB T6G 2S2, Canada.
3 enGene, Inc., Edmonton, AB T6G 2T5, Canada.
4 Department of Medicine, University of Tennessee, Memphis, TN 38103, USA.
5 Section of Gastroenterology, Boston Medical Center, Boston, MA 02118, USA.
*   To whom correspondence should be addressed. E-mail: tim.kieffer{at}ualberta.ca

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Science. ISSN 0036-8075 (print), 1095-9203 (online)