{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T19:49:31Z","timestamp":1760644171712,"version":"3.40.5"},"reference-count":20,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells Tissues Organs"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:p>Despite various efficient pharmaceuticals which are already used to manage diabetes, new drugs are needed to preserve and restore the function of pancreatic \u03b2-cells (p\u03b2Cs) including cell-specific gene expression and insulin production and secretion. Newly developed small molecules (SMs) with potential anti-diabetic activity need to be preliminarily tested. Mice insulinoma MIN6 cells can be utilized as an in vitro screening model. These cells have p\u03b2C characteristics and can secrete insulin in response to glucose level changes. As well, the \u03b2-cell-specific gene expression pattern of these cells is similar to that of mouse pancreatic islet cells. It is possible to use this cell line as a research tool to study the function of p\u03b2Cs. To date, approximately 60 genes have been identified which are effective in the p\u03b2C embryonic development and insulin production and secretion during puberty, including pancreas\/duodenum homeobox protein 1 (Pdx1), neuronal differentiation 1 (Neurod1), neurogenin3 (Ngn3), and insulin-1 precursor (Ins1). In this study, a family of new SMs that are structurally similar to glinides was synthesized through 3 different synthetic methods and categorized into 3 categories (C1\u2013C3). Then, these novel SMs were characterized by testing their effects on cell viability, p\u03b2C-specific gene expression, and insulin secretion in MIN6 in 4 different concentrations and at 3 time points (24, 48, and 72 h). According to our results, SMs of C1 (1j, 1k, and 1l) and 2 SMs of C3 (1f, 1i), at 200 \u03bcM concentration, were able to increase the expression levels of Pdx1, Neurod1, Ngn3, and Ins1 as well as the insulin secretion after 24 h. However, C2 (1a, 1b, 1c, and 1d) did not show significant bioactivity of MIN6 cells. These investigated molecules can provide a tool for exploring pseudo-islet functionality in MIN6 cells or provide a possible basis for future therapeutic interventions for diabetes. <\/jats:p>","DOI":"10.1159\/000522154","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T22:00:34Z","timestamp":1643061634000},"page":"220-231","source":"Crossref","is-referenced-by-count":3,"title":["Synthetic Small Molecules Induce Insulin Secretion and Pancreatic Beta-Cell-Specific Gene Expression"],"prefix":"10.1159","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-1453","authenticated-orcid":false,"given":"Mohammad","family":"Rabiei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8870-8035","authenticated-orcid":false,"given":"Naser","family":"Kalhor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisan","family":"Farhadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sorour","family":"Ramezanpour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaser","family":"Tahamtani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahnaz","family":"Azarnia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2003.12.001"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2017.03.007"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2017.06.019"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118526109"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2011.10.002"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/b978-0-12-818349-6.00001-7"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3789-z"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1111"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.2217\/rme.12.33"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmx008"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.medidd.2020.100075"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2327"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1177\/1479164119827611"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1242\/dev.093187"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1007\/s00706-017-2086-6"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20215417"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2018.03.025"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2019.04.063"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/925143"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1207-4"}],"container-title":["Cells Tissues Organs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/cto\/article-pdf\/212\/3\/220\/3952728\/000522154.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/cto\/article-pdf\/212\/3\/220\/3952728\/000522154.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:47:54Z","timestamp":1745423274000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000522154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":20,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,6,1]]},"published-print":{"date-parts":[[2023,5,26]]}},"URL":"https:\/\/doi.org\/10.1159\/000522154","archive":["Portico"],"relation":{},"ISSN":["1422-6405","1422-6421"],"issn-type":[{"type":"print","value":"1422-6405"},{"type":"electronic","value":"1422-6421"}],"subject":[],"published":{"date-parts":[[2022,1,24]]}}}