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Dimethyl carbonate (DMC) is a widely used industrial chemical, which may be increasingly used in the future. However, its toxicity profile remains largely unknown. The present study was designed to investigate the effects of DMC exposure on the ovaries and the effect of autophagy activation on follicular development. Rats were randomly divided into a control group and low, medium and high dose DMC groups (all n=10). Histological analyses identified no marked differences in the rate of apoptosis between the control and low dose groups; however, marked apoptosis occurred in the medium and high dose groups. The expression of cleaved caspase-3 was significantly increased in the medium and high dose groups, which was consistent with changes observed in the expression of Bcl-2 and Bax. These results indicated that DMC exposure induces toxicity on ovarian function via the induction of apoptosis. The increased expression of the autophagy-related proteins light chain 3II, beclin-1 and p62 following exposure to DMC further indicated that autophagy was activated primarily in the granulosa cells of ovarian follicles in a dose-dependent manner. In addition, the changes in the expression of hypoxia inducible factor 1 α subunit (HIF-1α) and its target protein BCL2 interacting protein 3 (BNIP3) indicated that they may serve a role in the follicular development process induced by DMC. The results of the current study demonstrated that DMC exposure activated autophagy in the ovarian tissue. Furthermore, exposure to low doses of DMC may protect follicular development by activating the HIF-1α/BNIP3 signaling pathway. Taken together, these results indicate that exposure to medium and high doses of DMC induced follicular atresia by activating the apoptotic signaling pathway. This may be an important mechanism of regulating follicular development and ovarian function in mammals.

Impaired glucose tolerance (IGT) is a pre-diabetic metabolic state involving heterogeneous and dynamic changes between the normal and diabetic state. The present study aimed to investigate the endocrine regulation of endothelium-dependent dysfunction in middle-aged patients with IGT and in patients with a normal glucose tolerance (NGT). An oral glucose tolerance test was performed to determine the NGT and IGT states. Physiological and biochemical analyses were performed. The carotid artery structure and function were investigated with Doppler supersonic diagnostic equipment. The functioning of the vascular endothelium was analyzed with physiological and biochemical indices in the IGT group. The results showed a significant reduction in endothelium-dependent vasodilation, but not in endothelium-independent vasodilation in the IGT group compared with those of the NGT group. It was identified that the intima-media thickness of the carotid artery and expression levels of endothelin-1 were significantly higher, whereas the endothelium-derived factor C-type natriuretic peptide levels were significantly lower in the IGT group compared with those in the NGT group. Notably, significant correlations were identified between endocrinological changes and body composition, including fat and glucose metabolism, in the IGT group. Our data indicate that vascular endothelial functions may be impaired by fat and glucose metabolism and body composition in IGT patients during prediabetes mellitusare.

Endothelial dysfunction (ED) is an early pathophysiological change in patients with impaired glucose tolerance (IGT) during prediabetes mellitus. This study was designed to test the hypothesis that exercise intervention contributes to the reversal of vascular endothelium-dependent dysfunction in middle-aged patients with IGT. Following exercise intervention, significant changes in endothelin (ET)-1, C-type natriuretic peptide (CNP), ΔDia-P, oral glucose tolerance test (OGTT)2h, fasting insulin, homeostasis model of assessment-insulin resistance (HOMA-IR), body fat percentage, waist circumference and waist to hip ratio were measured. However, no marked changes in carotid artery intima-media thickness (IMT), fasting blood glucose and BMI were observed following exercise intervention. Validity analysis of index changes in the two exercise intervention groups further confirmed there was no change. Exercise intervention increased CNP levels, decreased ET-1 levels and increased ΔDia-P, indicating improved vascular endothelium function. Decreased HOMA-IR following exercise suggests enhanced insulin sensitivity. Exercise intervention also improved glucose metabolism via decreased OGTT2h and fasting insulin. In addition, decreased waist circumference, ratio of waist to hip and body fat percentage following exercise intervention improved changes of body composition, including BMI, body fat and waist circumference. These results indicate that exercise intervention may reverse vascular endothelium-dependent dysfunction in middle-aged patients with IGT. This study also provided direct clinical data supporting the use of exercise intervention to prevent diabetes mellitus (DM) during the early stage.

Previous studies by our group have indicated that exercise intervention can ameliorate endothelial dysfunction, which is an early pathophysiological change of prediabetes mellitus. The present study aimed to test the hypothesis that nitric oxide synthases (NOSs), which are expressed in blood vessel endothelium, contribute to the mitigation of vascular endothelium-dependent dysfunction by aerobic exercise in prediabetes mellitus. A prediabetic rat model was established by feeding the rats an additional high-energy diet, and was confirmed by testing blood glucose levels, the area-under-the-curve for the blood glucose tests (P