{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:45:58Z","timestamp":1791297958879,"version":"4.1.0"},"reference-count":0,"publisher":"American Diabetes Association","issue":"12","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,12,1]]},"abstract":"<jats:p>The physiological role of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins in insulin exocytosis has been reported in pancreatic beta-cells. To determine whether the beta-cells of GK rats, a nonobese rodent model of type 2 diabetes, exhibit abnormalities in their SNARE proteins, we studied the expression and function of target (t)-SNAREs, syntaxin 1A, and synaptosomal-associated protein of 25 kDa (SNAP-25) in GK rat islets. Although insulin release and insulin content of islets isolated from 12-week-old GK rats were reduced, the proinsulin biosynthetic rate was about twofold higher than that in control rat islets, and no change in the preproinsulin mRNA level was observed. Pulse-chase experiments suggested the increased degradation of insulin in GK rat islets. Immunoblot analysis revealed that protein levels of syntaxin 1A and SNAP-25 in GK rat islets decreased to approximately 60% of the levels in control rat islets. We then examined whether the restoration of the decreased expression of t-SNAREs to the normal level in GK rat islets affected insulin secretion. Restoration was achieved by the overexpression of syntaxin 1A and SNAP-25 via the recombinant adenovirus-mediated gene transduction system, which recovered levels of these proteins to almost control levels. Glucose-stimulated insulin release from AdexlCA syntaxin 1A and Adex1CA SNAP-25-infected GK rat islets increased up to approximately 135 and 200%, respectively, of those from uninfected GK rat islets, although no difference in basal (2.2 mmol\/l glucose) insulin release was evident between them. We conclude that decreased expression of t-SNAREs in GK rat islets is in part the defect responsible for impaired insulin secretion.<\/jats:p>","DOI":"10.2337\/diabetes.48.12.2367","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T14:04:22Z","timestamp":1173189862000},"page":"2367-2373","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":154,"title":["Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion."],"prefix":"10.2337","volume":"48","author":[{"given":"S","family":"Nagamatsu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Nakamichi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Ozawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo, Japan. shinya@kyorin-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/48\/12\/2367\/364085\/10580425.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/48\/12\/2367\/364085\/10580425.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T12:46:42Z","timestamp":1667393202000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/48\/12\/2367\/10111\/Decreased-expression-of-t-SNARE-syntaxin-1-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12,1]]},"references-count":0,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1999,12,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.48.12.2367","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,12,1]]}}}