Diabetes, Vol 43, Issue 3 341-350, Copyright © 1994 by American Diabetes Association
Cellular engineering and gene therapy strategies for insulin replacement in diabetes
CB Newgard
Gillford Laboratories for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235.
In diabetes, insulin secretion is either completely absent
(insulin-dependent diabetes mellitus [IDDM]) or inappropriately regulated
(non-insulin-dependent diabetes mellitus [NIDDM]). In recent years, new
insights into the molecular and biochemical mechanism(s) of fuel-mediated
insulin release coupled with advances in gene transfer technology have led
to the investigation of molecular strategies for replacement of normal
insulin delivery function. Such initiatives have included attempts to
engineer glucose-stimulated insulin secretion in cell lines that might
serve as surrogates for islets in IDDM. The development of DNA virus gene
transfer systems of remarkable efficiency also has suggested ways in which
the beta-cell dysfunction of NIDDM might ultimately be repaired by gene
therapy. The emerging work in these areas and implications for the future
are summarized in this perspective.