{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:51:10Z","timestamp":1761519070689},"reference-count":0,"publisher":"American Diabetes Association","issue":"3","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,3,1]]},"abstract":"<jats:p>We determined the metabolic effects of insulin derived from renal subcapsular islet grafts, either with systemic delivery of insulin through renal venous drainage (REN) or with portal delivery of insulin after renal vein\u2013to\u2013superior mesenteric vein anastomosis (RMA), in streptozotocin-induced diabetic Lewis rats, in comparison with normal rats. After gavage glucose, the plasma glucose responses were similar to normal in REN and RMA rats; however, hyperinsulinemia occurred in REN rats (area under the concentration curves [AUCs] of insulin, 27 \u00b1 3 nmol \u00b7 l\u22121 \u00b7 min) in comparison with RMA (14 \u00b1 2) and normal rats (19 \u00b1 2), P &amp;lt; 0.003, with no difference in C-peptide responses. The ratio of AUC C-peptide to AUC insulin was lower in REN (2.0 \u00b1 0.2) than in RMA (3.4 \u00b1 0.3) and normal animals (3.2 \u00b1 0.3), P &amp;lt; 0.0005. In euglycemic-hyperinsulinemic clamp studies using the same insulin infusion rate (10 pmol \u00b7 kg\u22121 \u00b7 min\u22121), insulin resistance was found in REN animals (mean glucose infusion rate [GIR], REN: 7.5 \u00b1 1.2; RMA: 12.0 \u00b1 1.2; normal: 12.7 \u00b1 1.0 mg \u00b7 kg\u22121 \u00b7 min\u22121; P &amp;lt; 0.008), with higher steady-state insulin levels in REN (554 \u00b1 63 pmol\/l) than in RMA (291 \u00b1 26) and normal rats (269 \u00b1 60), P &amp;lt; 0.0001. With matching steady-state insulin levels in RMA and REN rats during infusion of insulin at 20 pmol \u00b7 kg\u22121 \u00b7 min\u22121 in RMA rats (steady-state insulin 623 \u00b1 64 pmol\/l), GIR was 15.7 \u00b1 0.7 mg \u00b7 kg\u22121 \u00b7 min\u22121. Thus, systemic delivery of insulin from islet grafts is associated with hyperinsulinemia, insulin resistance, and decreased metabolic clearance of insulin. These abnormalities are prevented by portal delivery of insulin from islet grafts in the same site. The findings are consistent with the hypothesis that portal delivery of insulin is important in maintenance of normal whole-body insulin sensitivity.<\/jats:p>","DOI":"10.2337\/diab.46.3.372","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:42:54Z","timestamp":1379612574000},"page":"372-378","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":12,"title":["Insulin Resistance Prevented by Portal Delivery of Insulin in Rats With Renal Subcapsular Islet Grafts"],"prefix":"10.2337","volume":"46","author":[{"given":"Jiayan","family":"Guan","sequence":"first","affiliation":[{"name":"Departments of Physiology, University of Western Ontario\u2008London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter F","family":"Zucker","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Western Ontario\u2008London, Ontario, Canada"},{"name":"John P. Robarts Research Institute\u2008London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret T","family":"Behme","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Western Ontario\u2008London, Ontario, Canada"},{"name":"Departments of Biochemistry, University of Western Ontario\u2008London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zhong","sequence":"additional","affiliation":[{"name":"Departments of Surgery, University of Western Ontario\u2008London, Ontario, Canada"},{"name":"John P. Robarts Research Institute\u2008London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Atkison","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, University of Western Ontario\u2008London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Dupr\u00e9","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Western Ontario\u2008London, Ontario, Canada"},{"name":"Departments of Physiology, University of Western Ontario\u2008London, Ontario, Canada"},{"name":"John P. Robarts Research Institute\u2008London, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/46\/3\/372\/362561\/46-3-372.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/46\/3\/372\/362561\/46-3-372.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:32:49Z","timestamp":1667406769000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/46\/3\/372\/9746\/Insulin-Resistance-Prevented-by-Portal-Delivery-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1997,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.46.3.372","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,3,1]]}}}