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Transient receptor potential channels have been put forward as regulators of insulin secretion. A role for the TRPV1 ion channel in insulin secretion has been suggested in pancreatic beta cell lines. We explored whether TRPV1 is functionally expressed in RINm5F and primary beta cells from neonate and adult rats. We examined if capsaicin could activate cationic non-selective currents. Our results show that TRPV1 channels are not functional in insulin-secreting cells, since capsaicin did not produce current activation, not even under culture conditions known to induce the expression of other ion channels in these cells. Although TRPV1 channels seem to be irrelevant for the physiology of isolated beta cells, they may play a role in glucose homeostasis acting through the nerve fibers that regulate islet function. At the physiological level, we observed that Trpv1 (-/-) mice presented lower fasting insulin levels than their wild-type littermates, however, we did not find differences between these experimental groups nor in the glucose tolerance test or in the insulin secretion. However, we did find that the Trpv1 (-/-) mice exhibited a higher insulin sensitivity compared to their wild-type counterparts. Our results demonstrate that TRPV1 does not contribute to glucose-induced insulin secretion in beta cells as was previously thought, but it is possible that it may control insulin sensitivity.

Transient receptor potential channels, especially the members of the melastatin family (TRPM), participate in insulin secretion. Some of them are substrates for protein kinases, which are involved in several neurotransmitter, incretin and hormonal signaling cascades in β cells. The functional relationships between protein kinases and TRPM channels in systems of heterologous expression and native tissues rise issues about novel regulation pathways of pancreatic β-cell excitability. The aim of the present work is to review the evidences about phosphorylation of TRPM channels in β cells and to discuss the perspectives on insulin secretion.

Cnidarians comprise a taxon with a high biodiversity of cytolitic, neurotoxic and cardiotoxic compounds, which have not been studied on insulin release. We tested the effect of a crude extract of Zoanthus sociatus (Ellis, 1767) and the low molecular weight fraction of this extract on insulin secretion in isolated rat β-cells and also in a glucose tolerance test in vivo. We observed that the extract inhibited insulin release by reducing the amount secreted by individual β-cells and also by silencing a fraction of the secreting population. This effect coincided with a diminished rise of intracellular Ca(+2) in response to high glucose and high K+ -induced depolarization. Moreover intraperitoneal administration of the low molecular weight fraction produced glucose intolerance in adult rats. The active fraction exhibited molecular weights similar to the neurotoxins described in the phylum. Our results broaden the toxic effects of cnidarian venoms and show evidence of potential modulators of voltage-gated Ca(+2) channels in this group., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Physalia physalis is a marine cnidarian from which high molecular weight toxins with hemolytic and neurotoxic effects have been isolated. In the present work, two novel toxins, PpV9.4 and PpV19.3 were purified from P. physalis by bioactive guideline isolation. It involved two steps of column chromatography, gel filtration and RP-HPLC. The molecular weights were 550.7 and 4720.9 Da for PpV9.4 and PpV19.3, respectively. In the light of the Edman sequencing results, the structure of these toxins included the presence of modified amino acids. Both toxins increased the percentage of insulin secreting beta-cells and induced cytosolic Ca2+ elevation. To date, this is the first report of low molecular weight toxins increasing insulin secretion purified from cnidarians, by constituting a new approach to the study of beta-cells physiology.

Glucose-induced insulin secretion is a cardinal process in glucose homeostasis and metabolic expenditure. Uncoupling of the insulin response to glucose variations may lead to type-2 diabetes mellitus. Thus the identification of more specific drugs to facilitate the study of insulin secretion mechanisms and to develop new pharmacological agents for therapeutics is fundamental. Venomous organisms possess a great diversity of toxic molecules and some of them are neurotoxins that affect membrane excitability. This article reviews properties of those toxins affecting ion channels pivotal for insulin secretion and the usefulness of such compounds in the study of pancreatic beta-cell physiology. Here we examine the major contributions of toxinology to the understanding of the ionic phase of insulin secretion, to the determination of ion channel composition in different insulin secreting cell-line models as well as from primary cultures of different mammal species. Finally, we present a summary of the many diverse toxins affecting insulin release and a brief discussion of the potential of novel toxins in therapeutics.