RNA sequencing of all transcripts and how islet β-cells fail

In this issue, Cnop et al. (1) report on using RNA-sequencing methodology and the response of the whole transcriptome of human islets to 48-h exposure to saturated free fatty acid (FFA) palmitate. They demonstrated that palmitate altered the expression of 1,325 genes and shifted alternate splicing of 3,525 transcripts. This follows on from a similar study by the same group on the effects on human islets of 48-h exposure to the proinflammatory cytokines interleukin-1b and interferon-g in which 3,065 (16%) of transcripts were modified and, again, alternate splicing of transcripts was commonly seen (2). However, islet b-cell failure causing diabetes, particularly type 2 diabetes, develops over years and not 48 h. So how do these technically remarkable in vitro experiments on human islets help us to understand islet b-cell failure?