Commiphora myrrha stimulates insulin secretion from mouse and human islets of Langerhans

Ethnopharmacological relevance: Traditionally plant-based remedies such as Commiphora myrrha (CM) have been used as an ayurvedic medicine to treat diabetes mellitus in some region of Arabia and Africa. Previous reports have shown that CM reduced blood glucose levels and increased insulin concentrations in animal models of diabetes in vivo. However, the exact mechanisms by which CM improved glycemic control in these animals are not fully understood. We hypothesized that CM may have a direct insulinotropic activity on beta-cells to increase insulin secretion. Aim of the study: The direct effects of CM were investigated using MIN6 beta-cells and isolated mouse and human islets in static and perifusion insulin secretion experiments. Isolated mouse and human islets were used to investigate the rate and pattern of CM-induced insulin secretion. Materials and methods: The effect of CM on insulin secretion was assessed by static and perifusion experiments using MIN6 cells, a mouse-derived beta-cell line, and primary mouse and human islets. The effects of CM on cell viability and membrane integrity of MIN6 cells and mouse islets were assessed using an ATP viability assay and a trypan blue exclusion test. The mRNA expression profiles of preproinsulin and Pdx1, a major beta-cell transcription factor, were determined by quantitative RT-PCR following chronic exposure to CM. Results: Exposing MIN6 cells to a CM resin solution (0.5-10 mg/ml) caused a concentration-dependent increase in insulin secretion in a static setting. Similarly, incubating mouse islets to CM (0.1-10 mg/ml) resulted in stimulation of insulin secretion in a concentration-dependent manner. CM concentrations at <= 2 mg/ml were not associated with reduction in cell viability nor with reduction in cell membrane integrity. However, higher concentrations of CM were accompanied with marked uptake of trypan blue dye and cell death. In a perifusion setting, CM (2 mg/ml) caused rapid and reversible increases in insulin secretion from both mouse and human islets at both sub-stimulatory and stimulatory glucose levels. The stimulatory effect of CM on insulin secretion did not change the total insulin content of beta-cells nor the mRNA expression of preproinsulin and Pdx1. Conclusions: These data indicate that aqueous CM resin solution has a direct stimulatory effect on beta-cells without compromising plasma membrane integrity. CM stimulates insulin secretion from MIN6 cells, a mouse-derived beta-cell line, and isolated primary mouse and human islets in vitro at both sub-stimulatory and stimulatory glucose concentrations. The mechanism by which CM may induce insulin secretion is most likely due to a stimulation of insulin granules release rather than insulin synthesis.