The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus

Background/Aims: Coenzyme Q₁₀ (CoQ₁₀) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ₁₀-based micelle formulation (CoQ₁₀-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). Methods: We developed CoQ₁₀-W from a glycyrrhizic-carnitine mixed layer CoQ₁₀ micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ₁₀ (CoQ₁₀-L) or CoQ₁₀-W for 4 weeks. Their plasma and pancreatic CoQ₁₀ concentrations were measured using liquid chromatography-tandem mass spectrometry. The therapeutic efficacies of CoQ₁₀-W and CoQ₁₀-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. Results: The plasma CoQ₁₀ level was significantly increased in the CoQ₁₀-W group compared to that in the CoQ₁₀-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ₁₀-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ₁₀-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ₁₀-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ₁₀-W than CoQ₁₀-L. Electron microscopy revealed that CoQ₁₀-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ₁₀-L. In vitro studies showed that CoQ₁₀-L and CoQ₁₀-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. Conclusions: CoQ₁₀-W has better therapeutic efficacy than CoQ₁₀-L in TAC-in-duced DM.