Abstract

Hydrogen sulfide (H₂S), a novel gasotransmitter, is involved in the regulation of gut motility. Alterations in the balance of H₂S play an important role in the pathogenesis of diabetes. This study was conducted to investigate the role of H₂S in the colonic hypomotility of mice with streptozotocin (STZ)-induced diabetes. A single intraperitoneal injection of STZ was used to induce the type 1 diabetes model. Male C57BL/6 mice were randomized into a control group and an STZ-treated group. Immunohistochemistry, Western blotting, H₂S generation, organ bath studies and whole-cell patch clamp techniques were carried out in single smooth muscle cells (SMCs) of the colon. We found that STZ-induced diabetic mice showed decreased stool output, impaired colonic contractility, and increased endogenous generation of H₂S (p < 0.05). H₂S-producing enzymes were upregulated in the colon tissues of diabetic mice (p < 0.05). The exogenous H₂S donor sodium hydrosulfide (NaHS) elicited a biphasic action on colonic muscle contraction with excitation at lower concentrations and inhibition at higher concentrations. NaHS (0.1 mM) increased the currents of voltage-dependent calcium channels (VDCCs), while NaHS at 0.5 mM and 1.5 mM induced inhibition. Furthermore, NaHS reduced the currents of both voltage-dependent potassium (K_V) channels and large conductance calcium-activated potassium (BK) channels in a dose-dependent manner. These results show that spontaneous contraction of colonic muscle strips from diabetic mice induced by STZ was significantly decreased, which may underlie the constipation associated with diabetes mellitus (DM). H₂S overproduction with subsequent suppression of muscle contraction via VDCCs on SMCs may contribute in part to the pathogenesis of colonic hypomotility in DM.