{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T22:51:58Z","timestamp":1767826318869,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["19K07139"],"award-info":[{"award-number":["19K07139"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["19H02837"],"award-info":[{"award-number":["19H02837"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Diabetes Foundation","award":["19K07139"],"award-info":[{"award-number":["19K07139"]}]},{"name":"Japan Diabetes Foundation","award":["19H02837"],"award-info":[{"award-number":["19H02837"]}]},{"name":"Joint Research Program of Juntendo University, Faculty of Health and Sports Science","award":["19K07139"],"award-info":[{"award-number":["19K07139"]}]},{"name":"Joint Research Program of Juntendo University, Faculty of Health and Sports Science","award":["19H02837"],"award-info":[{"award-number":["19H02837"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Differentiation-inducing factor 1 (DIF-1) isolated from the cellular slime mold Dictyostelium discoideum can inhibit mammalian calmodulin-dependent cAMP\/cGMP phosphodiesterase (PDE1) in vitro. DIF-1 also promotes glucose uptake, at least in part, via a mitochondria- and AMPK-dependent pathway in mouse 3T3-L1 fibroblast cells, but the mechanism underlying this effect has not been fully elucidated. In this study, we investigated the effects of DIF-1 on intracellular cAMP and cGMP levels, as well as the effects that DIF-1 and several compounds that increase cAMP and cGMP levels have on glucose uptake in confluent 3T3-L1 cells. DIF-1 at 20 \u03bcM (a concentration that promotes glucose uptake) increased the level of intracellular cAMP by about 20% but did not affect the level of intracellular cGMP. Neither the PDE1 inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine at 10\u2013200 \u03bcM nor the broad-range PDE inhibitor 3-isobutyl-1-methylxanthine at 40\u2013400 \u03bcM had any marked effects on glucose uptake. The membrane-permeable cAMP analog 8-bromo-cAMP at 200\u20131000 \u03bcM significantly promoted glucose uptake (by 20\u201325%), whereas the membrane-permeable cGMP analog 8-bromo-cGMP at 3\u2013100 \u03bcM did not affect glucose uptake. The adenylate cyclase activator forskolin at 1\u201310 \u03bcM promoted glucose uptake by 20\u201330%. Thus, DIF-1 may promote glucose uptake by 3T3-L1 cells, at least in part, via an increase in intracellular cAMP level.<\/jats:p>","DOI":"10.3390\/molecules28237926","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T05:28:21Z","timestamp":1701667701000},"page":"7926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacological Evidence That Dictyostelium Differentiation-Inducing Factor 1 Promotes Glucose Uptake Partly via an Increase in Intracellular cAMP Content in Mouse 3T3-L1 Cells"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9231-9833","authenticated-orcid":false,"given":"Yuzuru","family":"Kubohara","sequence":"first","affiliation":[{"name":"Laboratory of Health and Life Science, Graduate School of Health and Sports Science, Juntendo University, Inzai 270-1695, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Department of Animal Risk Management, Faculty of Risk and Crisis Management, Chiba Institute of Science, Choshi 288-0025, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-0185","authenticated-orcid":false,"given":"Haruhisa","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Division of Natural Medicines, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4362-0790","authenticated-orcid":false,"given":"Hidekazu","family":"Kuwayama","sequence":"additional","affiliation":[{"name":"Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1073\/pnas.58.3.1152","article-title":"The acrasin activity of adenosine-3\u2019,5\u2019-cyclic phosphate","volume":"58","author":"Konijn","year":"1967","journal-title":"Proc. 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