Diabetes mellitus (DM) is a very serious disease, the incidence of which has been increasing worldwide. The beginning of diabetic research can be traced back to the 17th century. Since then, animals have been experimented on for diabetic research. However, the greatest development of diabetes research occurred in the second half of the last century, along with the development of laboratory techniques. Information obtained by monitoring patients and animal models led to the finding that there are several types of DM that differ significantly from each other in the causes of the onset and course of the disease. Through different types of animal models, researchers have studied the pathophysiology of all types of diabetic conditions and discovered suitable methods for therapy. Interestingly, despite the unquestionable success in understanding DM through animal models, we did not fully succeed in transferring the data obtained from animal models to human clinical research. On the contrary, we have observed that the chances of drug failure in human clinical trials are very high. In this review, we will summarize the history and presence of animal models in the research of DM over the last hundred years. Furthermore, we have summarized the new methodological approaches, such as “organ-on-chip,” that have the potential to screen the newly discovered drugs for human clinical trials and advance the level of knowledge about diabetes, as well as its therapy, towards a personalized approach.

Neurogastroenterology, a rapidly evolving field, investigates the intricate interactions between the nervous system and the organs of the gastrointestinal tract. This review offers a comprehensive summary of innervation of the gastrointestinal tract, focusing on both extrinsic and intrinsic components. Extrinsic innervation involves the autonomic nervous system, with sympathetic and parasympathetic fibers controlling various digestive functions, while intrinsic innervation, represented by the enteric nervous system, operates largely independently, orchestrating complex processes such as motility, secretion, and immune responses. Recent advances highlight the crucial role of the enteric nervous system, often referred to as the second brain, in maintaining gastrointestinal health and its involvement in various pathologies. The text also provides a basic overview of the pathophysiology of achalasia, Chagas disease, gastroesophageal reflux disease, gastroparesis, diabetic gastroenteropathy, irritable bowel syndrome, chronic intestinal pseudo-obstruction, and Hirschsprung's disease, which are conditions in which innervation of the gastrointestinal tract is more or less affected. The insights provided could pave the way for new interventions, offering hope for patients suffering from related conditions.

Background: The neuropeptide B/W signalling system (NPB/W) has been identified in multiple body regions and is integral to several physiological processes, including the regulation of food intake and energy homeostasis. Recently, it has also been detected in human skin; however, its specific functions in this context remain to be thoroughly investigated. This study aims to identify the expression of neuropeptides B/W receptor 1 (NPBWR1) and neuropeptides B/W receptor 2 (NPBWR2) in human dermal fibroblasts of mesenchymal origin using genomic and proteomic techniques. We will also investigate the role of these receptors in cell proliferation and calcium signalling. Methods: The mRNAs for NPBWR1 and NPBWR2 were detected using quantitative PCR (qPCR) analysis and further validated by western blot and immunofluorescence analyses. Additionally, we synthesised ligands for these receptors, specifically hNPB (25–53) and hNPW (33–62), to investigate their effects on cell proliferation and intracellular calcium levels in human fibroblasts. Results: Our results demonstrated that hNPW (33–62) has anti-proliferative effect on human dermal fibroblasts and concentration of 0.1-μmol/L can significantly decrease intracellular calcium levels (p < 0.05). Conclusion: This finding suggests a potential role for the NPB/W signalling system in pathologies associated with impaired calcium handling, such as fibrosis. Furthermore, we observed that the proliferation of human fibroblasts was not affected by hNPB (25–53). Our findings could lead to the development of new therapeutic strategies for various skin conditions and improved wound healing.

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.