{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:56Z","timestamp":1784557136725,"version":"3.55.0"},"reference-count":43,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>\n                    Glucokinase (GK) plays a critical role in controlling blood glucose; GK activators have been shown to stimulate insulin secretion acutely both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Sustained stimulation of insulin secretion could potentially lead to \u03b2-cell exhaustion; this study examines the effect of chronic GK activation on \u03b2-cells. Gene expression and insulin secretion were measured in rodent islets treated\n                    <jats:italic>in vitro<\/jats:italic>\n                    with GKA71 for 72\u200ah. Key \u03b2-cell gene expression was measured in rat, mouse and global GK heterozygous knockout mouse islets (\n                    <jats:italic>gk<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>del\/wt<\/jats:italic>\n                    <\/jats:sup>\n                    ). Insulin secretion, after chronic exposure to GKA71, was measured in perifused rat islets. GKA71 acutely increased insulin secretion in rat islets in a glucose-dependent manner. Chronic culture of mouse islets with GKA71 in 5\u200ammol\/l glucose significantly increased the expression of insulin, IAPP, GLUT2, PDX1 and PC1 and decreased the expression of C\/EBP\u03b2 compared with 5\u200ammol\/l glucose alone. Similar increases were shown for insulin, GLUT2, IAPP and PC1 in chronically treated rat islets. Insulin mRNA was also increased in GKA71-treated\n                    <jats:italic>gk<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>del\/wt<\/jats:italic>\n                    <\/jats:sup>\n                    islets. No changes in\n                    <jats:italic>GK<\/jats:italic>\n                    mRNA were observed. Glucose-stimulated insulin secretion was improved in perifused rat islets following chronic treatment with GKA71. This was associated with a greater insulin content and GK protein level. Chronic treatment of rodent islets with GKA71 showed an upregulation of key \u03b2-cell genes including insulin and an increase in insulin content and GK protein compared with glucose alone.\n                  <\/jats:p>","DOI":"10.1530\/jme-10-0157","type":"journal-article","created":{"date-parts":[[2011,5,13]],"date-time":"2011-05-13T22:19:48Z","timestamp":1305325188000},"page":"59-67","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":9,"title":["Upregulation of \u03b2-cell genes and improved function in rodent islets following chronic glucokinase activation"],"prefix":"10.1530","volume":"47","author":[{"given":"D","family":"Gill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K J","family":"Brocklehurst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H W G","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D M","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"issue":"3","key":"1_18859946","doi-asserted-by":"publisher","first-page":"275","DOI":"10.2174\/1566524053766004","volume":"5","author":"Ahr\u00a0\u00a0n","year":"2005","journal-title":"Current molecular medicine","ISSN":"https:\/\/id.crossref.org\/issn\/1566-5240","issn-type":"print"},{"issue":"2","key":"2_16563716","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1006\/bbrc.1996.1826","volume":"229","author":"Aizawa","year":"1996","journal-title":"Biochemical and biophysical research communications","ISSN":"https:\/\/id.crossref.org\/issn\/0006-291X","issn-type":"print"},{"issue":"1","key":"3_19279202","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bbaexp.2005.05.009","volume":"1730","author":"Aramata","year":"2005","journal-title":"Biochimica et Biophysica Acta. 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