INS-1 cells were treated with different
concentrations of testosterone and examined at different time points. In contrast to control, excess testosterone treatment for 48 h could promote glucose-stimulated insulin secretion and enhance pancreatic/duodenal homeobox-1 and glucose transporter-2 mRNA expression up to 2-fold. Alternatively, long-time and high-concentration testosterone treatment significantly impaired glucose-stimulated insulin secretion and insulin mRNA levels and promoted malondialdehyde content. Androgen receptor antagonist flutamide could partly Caspase activity assay attenuate glucose-stimulated insulin secretion. These results indicate that direct in vitro exposure of INS-1 cells to testosterone had both concentration- and time-dependent effects on glucose-stimulated insulin secretion, gene expression, and oxidative stress. These findings showed to some extent that excess circulation of testosterone might impair beta-cell function, and further contribute to the etiology of insulin resistance in polycystic ovary syndrome.”
“Significance: The formation and degradation of S-nitrosothiols (SNOs) are important mechanisms of post-translational protein modification and appear to be ubiquitous in biology. These processes play well-characterized roles in eukaryotic cells, including a variety of pathologies and in relation to chronic conditions. We know little of the roles
of these processes in pathogenic and other bacteria. Recent Advances: It is clear, mostly from growth and transcriptional studies, that bacteria sense and respond to exogenous SNOs. These responses are phenotypically and mechanistically BX-795 in vitro distinct from the responses of bacteria to nitric oxide (NO) and NO-releasing agents, as well as peroxynitrite. Small SNOs, such as S-nitrosoglutathione (GSNO), are accumulated by bacteria with the result
that intracellular S-nitrosoproteins (the ‘S-nitrosoproteome’) are detectable. Recently, conditions for endogenous SNO formation in enterobacteria have been described. Critical Issues: The propensity of intracellular proteins to form SNOs is presumably constrained by the same rules of JNK-IN-8 nmr selectivity that have been discovered in eukaryotic systems, but is also influenced by uniquely bacterial NO detoxification systems, exemplified by the flavohemoglobin Hmp in enterobacteria and NO reductase of meningococci. Furthermore, the bacterial expression of such proteins impacts upon the formation of SNOs in mammalian hosts. Future Directions: The impairment during bacterial infections of specific SNO events in the mammalian host is of considerable interest in the context of proteins involved in innate immunity and intracellular signalling. In bacteria, numerous mechanisms of S-nitrosothiol degradation have been reported (e.g., GSNO reductase); others are thought to operate, based on consideration of their mammalian counterparts.