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Transplantation and Autoimmunity Branch, National Institute of Diabetes, Digestive and Kidney Diseases (A.S., S.C.H., B.H., D.M.H.) and Basic Research Laboratory, National Cancer Institute (C.A.P., M.R., J.N.B.) National Institutes of Health, Bethesda, Maryland 20889-5603
Human pancreatic islets are a major focus of diabetes research due
to their key role in glucose homeostasis and their potential for
transplantation in the treatment of type 1 diabetes. Currently, no
comprehensive analysis of baseline or glucose-stimulated islet gene
expression is available. Using oligonucleotide microarrays we analyzed
isolated intact human islets incubated at low and high glucose. We
identified 
6000 islet genes, several with clinical implications, as
well as a number of glucose-regulated genes. Interestingly, two
transforming growth factor ß (TGFß) superfamily members were highly
regulated by glucose. One of them, PDF, was found to have a very high
expression level compared to other TGFß superfamily members.
Quantitative reverse transcriptase polymerase chain reaction confirmed
these results and demonstrated that the highly expressed PDF was
10-fold down- regulated by glucose while other TGFß
superfamily members and target genes were up-regulated. These results
suggest that a highly regulated TGFß signaling cascade exists in
human islets, and that PDF may play a central role in islet biology.
Since TGFß is involved in differentiation and immune modulation, this
novel pathway may link glucose metabolism, immune response and
development of human islets. We report here the first gene expression
profile of intact human islets. These and similar analyses will provide
better understanding of human islet biology and enhance the development
of novel diabetes therapies.
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