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Loss of ARNT/HIF1Beta Mediates Altered Gene Expression and
Pancreatic-Islet Dysfunction in Human Type 2 Diabetes
J.E. Gunton, R.N. Kulkarni, S. Yim, T. Okada, W.J. Hawthorne, Y.-H.
Tseng, R.S. Roberson, C. Ricordi, P.J. O’Connell, F.J. Gonzalez, and
C.R. Kahn Source: http://www.cell.com/cgi/content/abstract/122/3/337
Type 2 diabetes is a worldwide epidemic characterized by failure of
the insulin producing beta cells. To understand the molecular basis
of this disease, Gunton et al. performed microarray analyses of
postmortem islets from people with type 2 diabetes. This revealed
multiple changes in gene expression including a marked decrease in
the transcription factor ARNT. Genetic knockout of ARNT in mice led
to beta cell failure and diabetes, as well as other changes in gene
expression similar to those in human diabetes. Thus, loss of ARNT
likely plays an important role in the development of human type 2
diabetes, and increasing level or activity may prevent or treat
diabetes.
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