Gastrointestinal expression of the NPB/W signaling system and inhibitory effects of neuropeptide B and W on colonic contractility in control and diabetic rats

Diabetic gastroenteropathy represents a frequent complication of diabetes mellitus, characterized by complex disturbances of gastrointestinal motility and neurochemical signaling. The neuropeptide B/W signaling system, consisting of neuropeptide B (NPB), neuropeptide W (NPW), and their receptors NPBWR1 and NPBWR2, has recently emerged as a potential modulator of metabolic and autonomic functions; however, its role within the gastrointestinal tract and its modulation by diabetes remains poorly understood. In this study, we systematically investigated the expression and functional relevance of the NPB/W signaling system along the gastrointestinal tract, using experimental models of type 1 and type 2 diabetes mellitus. Adult lean Zucker rats, streptozotocin-treated rats, and Zucker Diabetic Fatty rats were examined at early and advanced stages of diabetes. Gene expression was assessed in multiple gastrointestinal regions using RT-qPCR, while protein expression and localization in the colon were also analyzed by Western blot and immunofluorescence. In addition, ex vivo colonic contractility was evaluated to determine functional responses to NPB and NPW. All components of the NPB/W signaling system were detected throughout the gastrointestinal tract. Diabetes induced region-specific and stage-dependent alterations in gene expression, with more pronounced changes observed in the insulin-deficient model. Both NPB and NPW exerted concentration-dependent inhibitory effects on colonic contractility. Taken together, our findings demonstrate that the NPB/W signaling system is an integral component of gastrointestinal regulation and is differentially affected by diabetes. These alterations may contribute to impaired colonic motility observed in diabetic gastroenteropathy and highlight the NPB/W pathway as a potential target for future therapeutic interventions.