Articles > Induction of insulin secretion in engineered liver cells by nitric oxide

Induction of insulin secretion in engineered liver cells by nitric oxide

Induction of insulin secretion in engineered liver cells by nitric oxide

Latha Muniappan and Sabire Özcan

Department
of Molecular and Cellular Biochemistry, College of Medicine, University
of Kentucky, 741 South Limestone, BBSRB, Lexington, KY 40536, USA

BMC Physiology 2007,
7:11. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.

 

Abstract

Background

Type 1 Diabetes Mellitus results from an autoimmune destruction of
the pancreatic beta cells, which produce insulin. The lack of insulin
leads to chronic hyperglycemia and secondary complications, such as
cardiovascular disease. The currently approved clinical treatments for
diabetes mellitus often fail to achieve sustained and optimal glycemic
control. Therefore, there is a great interest in the development of
surrogate beta cells as a treatment for type 1 diabetes. Normally,
pancreatic beta cells produce and secrete insulin only in response to
increased blood glucose levels. However in many cases, insulin
secretion from non-beta cells engineered to produce insulin occurs in a
glucose-independent manner. In the present study we engineered liver
cells to produce and secrete insulin and insulin secretion can be
stimulated via the nitric oxide pathway.

Results

Expression of either human insulin or the beta cell specific
transcription factors PDX-1, NeuroD1 and MafA in the Hepa1-6 cell line
or primary liver cells via adenoviral gene transfer, results in
production and secretion of insulin. Although, the secretion of insulin
is not significantly increased in response to high glucose, treatment
of these engineered liver cells with L-arginine stimulates insulin
secretion up to three-fold. This L-arginine-mediated insulin release is
dependent on the production of nitric oxide.

Conclusion

Liver cells can be engineered to produce insulin and insulin
secretion can be induced by treatment with L-arginine via the
production of nitric oxide.

 


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