Figure 6.

Diagram for the possible mechanisms of the protective effects of dapagliflozin on GM-plasma-testis tissue axis. For db mice, the altered GM abundances in intestine, especially L. johnsonii, were closely related to the changed cecal adenosine metabolism; subsequently, the metabolized cAMP entered into circulation, resulting in the aberrant plasmatic cAMP enrichment and testicular 2′-deoxyinosine. Dapagliflozin administration could alleviate apoptosis and oxidative stress in the testis tissues by down-regulating the intensity of 2′-deoxyinosine, thus improved spermatogenesis of db/db diabetic mice. Taken together, we suggest that the protective effect of dapagliflozin on spermatogenetic aberrance is associated with the GM-plasma-testis regulatory axis.