TRP-ing Down the Path to Insulin Secretion

  1. Patrick E. MacDonald
  1. From the Alberta Diabetes Institute and Department of Pharmacology, University of Alberta, Edmonton, Canada.
  1. Corresponding author: Patrick MacDonald, pmacdonald{at}pmcol.ualberta.ca.

The means by which glucose stimulates insulin secretion from pancreatic β-cells has been studied for decades. Yet we still do not fully understand the cellular machinery underlying this process, the complexity of which continues to surprise. The triggering pathway for glucose-induced insulin secretion is generally well described, and the current model, shown on the left-side of Fig. 1, has been accepted for more than 20 years (1,2). However, it is abundantly clear that the ion channels currently included in this consensus model are insufficient to describe the complicated electrophysiological and intracellular Ca2+ responses of the β-cell to glucose and other secretagogues. Furthermore, the contribution of an ion channel-based component to the well-known “amplifying” effects of glucose (3) remains unclear. Recent studies, including that of Uchida et al. (4) in the present issue, are beginning to elucidate roles for multiple additional ion channels in the β-cell electrical and intracellular Ca2+ responses, particularly the contribution of the transient receptor potential (TRP) channels. Moreover, there are hints that these channels may play a more complex role in β-cells than we suspect.

FIG. 1.

TRPM channels in insulin secretion. On the left is the consensus triggering pathway for insulin secretion in which a glucose-stimulated rise in the ATP/ADP ratio closes ATP-sensitive K+ (KATP) channels, depolarizing the β-cell and activating voltage-gated Na+ (NaV) and Ca2+ (CaV) channels. The latter mediates Ca2+ influx that triggers insulin granule exocytosis. On the right are TRPM channels shown to contribute to β-cell Ca2+ and insulin responses. TRPM4 and (perhaps to a greater degree) TRPM5 mediate …

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