Canatoxin, a plant protein, induces insulin release from isolated pancreatic islets

Canatoxin (CNTX), the toxic protein purified from Canavalia ensiformis, has been shown to induce secretion from different cellular systems through a mechanism involving a lipoxygenase-mediated pathway. Here it is shown that CNTX causes insulin release from isolated rat pancreatic islets. This effect is time and dose dependent, occurs in the absence as well in the presence of glucose, and is markedly reduced at lower temperatures (15 C). At 1-2 microM, the insulinotropic effect of CNTX is equivalent to that of 20 mM glucose, and the two responses are not additive. The stimulatory effect of CNTX is not caused by a toxic or lytic effect of the toxin on the islets, since islets once exposed to CNTX are able to respond a new insulinotropic stimulus. The phospholipase inhibitor mepacrine impairs insulin release induced by either CNTX or glucose. Indomethacin, an inhibitor of the cyclooxygenation of arachidonic acid, fails to affect insulin release, but two lipoxygenase inhibitors block it, and epinephrine reduces it. These data suggest that CNTX may act on islets through the same pathway as that used by glucose, with both effects being mediated by lipoxygenases.