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Several mediators and mechanisms are known to be involved in the regulation of \u03b2 cell secretory function. In this study, we propose that cytokine-induced nitric oxide (NO) production interacts with cholinergic mechanisms to modulate insulin secretion from pancreatic \u03b2 cells. Using a rat insulinoma cell line INS-1, we demonstrated that \u03b2 cell viability decreases significantly in the presence of SNAP (NO donor) in a concentration- and time-dependent manner. Cell viability was also found to be decreased in the presence of a combined treatment of SNAP with SMN (muscarinic receptor antagonist). We then investigated the impact of these findings on insulin secretion and found a significant reduction in glucose uptake by INS-1 cells in the presence of SNAP and SMN as compared with control. Nitric oxide synthase 3 gene expression was found to be significantly reduced in response to combined treatment with SNAP and SMN suggesting an interaction between the cholinergic and nitrergic systems. The analysis of gene and protein expression further pin-pointed the involvement of M<jats:sub>3<\/jats:sub> muscarinic receptors in the cholinergic pathway. Upon treatment with cytokines, reduced cell viability was observed in the presence of TNF-\u03b1 and IFN-\u03b3. A significant reduction in insulin secretion was also noted after treatment with TNF-\u03b1 and IFN-\u03b3 and IL1-\u03b2. The findings of the present study have shown for the first time that the inhibition of the excitatory effects of cholinergic pathways on glucose-induced insulin secretion may cause \u03b2 cell injury and dysfunction of insulin secretion in response to cytokine-induced NO production.<\/jats:p>","DOI":"10.1007\/s00424-020-02443-9","type":"journal-article","created":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T23:36:13Z","timestamp":1597534573000},"page":"1469-1480","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nitric oxide interacts with cholinoceptors to modulate insulin secretion by pancreatic \u03b2 cells"],"prefix":"10.1007","volume":"472","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1554-6319","authenticated-orcid":false,"given":"Bashair M.","family":"Mussa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankita","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul Khader","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J. 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