Progesterone has been associated with the development of gestational diabetes (GD) due to the enhancement of insulin resistance. As b-cell apoptosis participates in type 1 and type 2 diabetes pathophysiology, we proposed the hypothesis that progesterone might contribute to the development of GD through a mechanism that also involves b-cell death. To address this question, RINm5F insulin-producing cells were incubated with progesterone (25-100 mM), in the presence or absence of a-tocopherol (40 mM). After 24 or 48 h, membrane integrity and DNA fragmentation were analyzed by flow cytometry. Caspase activity was used to identify the mode of cell death. The involvement of endoplasmic reticulum stress in the action of progesterone was investigated by western blotting. Oxidative stress was measured by 2',7'-dichlorofluorescein diacetate (DCFDA) oxidation. Isolated rat islets were used in similar experiments in order to confirm the effect of progesterone in primary b-cells. Incubation of RINm5F cells with progesterone increased the number of cells with loss of membrane integrity and DNA fragmentation. Progesterone induced generation of reactive species. Pre-incubation with a-tocopherol attenuated progesterone-induced apoptosis. Western blot analyses revealed increased expression of CREB2 and CHOP in progesteronetreated cells. Progesterone caused apoptotic death of rat islet cells and enhanced generation of reactive species. Our results show that progesterone can be toxic to pancreatic b-cells through an oxidative-stress-dependent mechanism that induces apoptosis. This effect may contribute to the development of GD during pregnancy, particularly under conditions that require administration of pharmacological doses of this hormone.
Fatty acid (FA) may disturb the redox state of the cells not only by an increase in reactive oxygen species (ROS) generation but also due to a reduction in antioxidant enzyme activities. The effect of various FAs (palmitic, stearic, oleic, linoleic, gamma-linolenic and eicosapentaenoic acids (EPAs)) on Jurkat and Raji cells, (human T and B leukaemic cell lines was investigated). The following measurements were carried out: FA composition of the cells, cell proliferation and activities of catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD). The protective effect of alpha-tocopherol on cell death was also investigated. Each cell line presented a specific FA composition. All the tested FAs reduced catalase activity. The toxic effect of FA was abolished by the pre-incubation with physiological concentrations of alpha-tocopherol. The findings support the proposition that the increase in oxidative stress induced by FA partially occurs due to a reduction in catalase activity. In spite of the decrease in the enzyme activity, catalase protein and mRNA levels were not changed, suggesting a post-translational regulation.
An important challenge for both students and teachers of physiology is to integrate the different areas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it comes to cuts in expenses. With the aim of addressing this kind of problem, the graduate students of our department organized a physiology summer course offered to undergraduate students. The objective was to present the different physiological systems in an integrated fashion. The strategy pursued was to plan laboratory classes whose experimental results were the basis for the relevant theoretical discussions. The subject we developed to illustrate physiology integration was the study of factors influencing salivary secretion.
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