In the pathophysiology of diabetes including mitochondrial diabetes, apoptosis of β-cells plays important roles in impaired insulin secretion. Although the detailed fundamental mechanism of CoQ10 in mitochondrial diabetes is unknown, therapeutic effects of CoQ10 on mitochondrial diabetes have been reported in several studies [
4]. We hypothesized that CoQ10 has protective effects against apoptosis in pancreatic β-cells. In this study, we induced apoptosis of MIN6 cells using STS, a mitochondrial stress agent [
9]. In WST-8 assays, 0.5 µM STS treatment for 16 h induced the death of about half of the cells. Although cell death might be caused by both apoptosis and necrosis, we showed translocation of PS from the inner leaflet to the outer leaflet of the MIN6 cell membrane, release of cytochrome c from mitochondria, activation of caspase-3, and DNA fragmentation of MIN6 cells. Therefore, MIN6 cell death induced by STS treatment was caused by apoptosis in this study. Based on these results, β-cells were protected by CoQ10 from apoptosis caused by STS treatment. In addition, this protective effect was equivalent to that of Z-VAD-FMK, an anti-apoptotic agent, suggesting that CoQ10 may be an effective anti-apoptotic agent. The fundamental effectiveness or mechanism of CoQ10 in mitochondrial diabetes have not been reported. However, the clinical effectiveness of CoQ10 against a central symptom of mitochondrial disease has been reported [
6]. The mechanism is an antioxidant action and stimulates ATP supply from mitochondria [
7]. In our study, CoQ10 had an anti-apoptotic action in β-cells. We believe that the protective mechanism of CoQ10 is a direct effect on mitochondria through ATP supply, but elucidation of the detailed mechanism is needed in the future. In mitochondrial diabetes, a hereditary disorder of mitochondrial functions causes impaired insulin secretion [
1]. Conversely, in type-2 diabetes, mitochondrial dysfunction caused by various kinds of stress, such as oxidative stress, plays important roles in the pathological progression [
10]. Hodgson et al. [
11] reported that CoQ10 treatment improves blood pressure and glycemic control in type-2 diabetes patients. This finding suggests that CoQ10 may have protective effects on pancreatic β-cells against mitochondrial stress in the clinic. In Japan, CoQ10 as a ubiquinone is applicable to insurance for heart failure, but not diabetes. However, CoQ10 is already generally used as a supplement. Therefore, if evidence that CoQ10 has effective effects on mitochondrial or type-2 diabetes accumulates, CoQ10 may be adopted clinically.
There are limitations in our study. First, STS treatment is non-physiological stimulation. Further studies are needed to clarify whether CoQ10 has protective effects against apoptosis induced by physiological stimulation. Second, we only investigated MIN6 cells. Experiments using an animal model are necessary to examine the clinical effectiveness of CoQ10. However, we revealed a part of the underlying mechanism of CoQ10 in protection of pancreatic β-cells from apoptosis caused by mitochondrial stress. Elucidation of the more detailed mechanism may facilitate clinical application of CoQ10.