Recent Advances in Molecular Research on Hydrogen Sulfide (H 2 S) Role in Diabetes Mellitus (DM)-A Systematic Review.

Abundant experimental data suggest that hydrogen sulfide (H 2 S) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including receptors, membrane ion channels, signalingmolecules, enzymes, and transcription factors, are known to be responsible for the H 2 S biological actions; however, H 2 S is not fully documented as a gaseous signaling molecule interfering with DM and vascular-linked pathology. In recent decades, multiple approaches regarding therapeutic exploitation of H 2 S have been identified, either based on H 2 S exogenous apport or on its modulated endogenous biosynthesis. This paper aims to synthesize and systematize, as comprehensively as possible, the recent literature-related data regarding the therapeutic/rehabilitative role of H 2 S in DM. This review was conducted following the "Preferred reporting items for systematic reviews and meta-analyses" (PRISMA) methodology, interrogating five international medically renowned databases by specific keyword combinations/"syntaxes" used contextually, over the last five years (2017-2021). The respective search/filtered and selection methodology we applied has identified, in the first step, 212 articles. After deploying the next specific quest steps, 51 unique published papers qualified for minute analysis resulted. To these bibliographic resources obtained through the PRISMA methodology, in order to have the best available information coverage, we added 86 papers that were freely found by a direct internet search. Finally, we selected for a connected meta-analysis eight relevant reports that included 1237 human subjects elicited from clinical trial registration platforms. Numerous H 2 S releasing/stimulating compounds have been produced, some being used in experimental models. However, very few of them were further advanced in clinical studies, indicating that the development of H 2 S as a therapeutic agent is still at the beginning.