Canavanine induces insulin release via activation of imidazoline I₃ receptors

Abstract

The aim of the present study was to identify the effect of canavanine on the imidazoline receptor because canavanine is a guanidinium derivative that has a similar structure to imidazoline receptor ligands. Transfected Chinese hamster ovary-K1 cells expressing imidazoline receptors (nischarin (NISCH)-CHO-K1 cells) were used to elucidate the direct effects of canavanine on imidazoline receptors. In addition, the imidazoline I3 receptor has been implicated in stimulation of insulin secretion from pancreatic β-cells. Wistar rats were used to investigate the effects of canavanine (0.1, 1 and 2.5 mg/kg, i.v.) on insulin secretion. In addition the a specific I3 receptor antagonist KU14R (4 or 8 mg/kg, i.v.) was used to block I3 receptors. Canavanine decreased blood glucose by increasing plasma insulin in rats. In addition, canavanine increased calcium influx into NISCH-CHO-K1 cells in a manner similar to agmatine, the endogenous ligand of imidazoline receptors. Moreover, KU12R dose-dependently attenuated canavanine-induced insulin secretion in HIT-T15 pancreatic β-cells and in the plasma of rats. The data suggest that canavanine is an agonist of I3 receptors both in vivo and in vitro. Thus, canavanine would be a useful tool in imidazoline receptor research.

Investigation of morin‐induced insulin secretion in cultured pancreatic cells

“…Therefore, NISCH seems suitable for use to indicate the imidazoline binding sites and I‐R without subtype specificity. In the present study, similar to another agonist, canavanine, the effects of morin were markedly reduced in MIN6 cells with ablated NISCH, indicating the important role of the I‐R in insulin secretion of morin. Moreover, this view is further supported by the effects of the negative control carbachol on insulin secretion, which was not changed in MIN6 cells with ablated NISCH.…”

“…In the present study, we demonstrated that KU14R can inhibit morin‐induced insulin secretion in MIN6 cells at a dose sufficient to block I‐3R . KU14R has been used as the antagonist of I‐3R in some reports .…”

“…The increase in insulin secretion induced by morin was markedly reduced in MIN6 cells lacking the I‐R (Figure A). Similarly, insulin secretion induced by another agonist, canavanine, was also ablated in the same manner. However, as shown in Figure A, effects of carbachol were not changed by the ablation of I‐R.…”

“…Pancreatic β‐cells exhibit exocytosis to release insulin via increased calcium ions . We also demonstrated that canavanine, another natural product, could activate I‐3R to increase insulin secretion . Similar to the effects of canavanine, morin may protect pancreatic islets from chemical damage .…”

Free Amino Acids, Including Canavanine, in the Seeds from 24 Wild Mediterranean Legumes

“…Thus, canavanine inhibits cell proliferation [20] and induces apoptosis [21,22] in cell cultures, and it also increases susceptibility to radiation in cancer cells [23]. In addition, it inhibits some of the deleterious effects of endotoxic shock in rat models [24,25] and has potential as an antidiabetic agent because it has been found to increase uptake of glucose [26] and release of insulin [27] in cell cultures.…”