ID’ing a Novel Inhibitor of β-Cell Function, Id1

  1. Nils Billestrup
  1. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
  1. Corresponding author: Nils Billestrup, billestrup{at}sund.ku.dk.

It is well established that loss of β-cell mass and compromised β-cell function are telltale indicators of the development of type 2 diabetes (1). Even individuals at risk for developing diabetes show β-cell dysfunction such as reduction of first-phase insulin release (2). An early response to increased insulin demand, as brought about in states of insulin resistance such as obesity or pregnancy, is a compensatory upregulation of the pancreatic β-cell mass and function. However, when this compensation fails and an inadequate amount of insulin is released in response to a meal, diabetes develops. The inability of β-cells to compensate for insulin resistance is associated with several abnormalities in β-cell function such as mitochondrial stress and reactive oxygen species production, insufficient proinsulin-to-insulin processing, and increased expression of islet amyloid polypeptide. Many of these abnormalities are believed to be the result of a combination of genetic and environmental factors. In particular, the exposure of β-cells to high concentrations of free fatty acids in combination with hyperglycemia (glucolipotoxicity) have been shown to be detrimental to β-cells resulting in severe dysfunction, loss of differentiation markers, and apoptosis. The detailed cellular and molecular mechanism by which β-cell dysfunction develops leading to type 2 diabetes is yet to be fully understood.

In a search for genes with altered expression in islets from diabetic mice, it was found that the mRNA level for the gene encoding the transcriptional regulator Id1 (inhibitor of DNA binding-1) was increased in islets from db/db mice (3), and furthermore, Id1 mRNA was increased in response to long-term exposure of β-cells to free fatty acids (4) as well as hyperglycemia (5). In order to investigate if Id1 plays …

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