{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:18:33Z","timestamp":1791983913947,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T00:00:00Z","timestamp":1562544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We previously quantified the hypoglycaemia\u2010sparing effect of portal vs peripheral human insulin delivery. The current investigation aimed to determine whether a bioequivalent peripheral vein infusion of a hepatopreferential insulin analog, insulin\u2010406, could similarly protect against hypoglycaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Dogs received human insulin infusions into either the hepatic portal vein (PoHI, n = 7) or a peripheral vein (PeHI, n = 7) for 180\u2009minutes at four\u2010fold the basal secretion rate (6.6 pmol\/kg\/min) in a previous study. Insulin\u2010406 (Pe406, n = 7) was peripherally infused at 6.0 pmol\/kg\/min, a rate determined to decrease plasma glucose by the same amount as with PoHI infusion during the first 60\u2009minutes. Glucagon was fixed at basal concentrations, mimicking the diminished \u03b1\u2010cell response seen in type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Glucose dropped quickly with PeHI infusion, reaching 41\u2009\u00b1\u20093 mg\/dL at 60\u2009minutes, but more slowly with PoHI and Pe406 infusion (67\u2009\u00b1\u20092 and 72\u2009\u00b1\u20094 mg\/dL, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01 vs PeHI for both). The hypoglycaemic nadir (\n                      <jats:italic>c<\/jats:italic>\n                      . 40\u2009mg\/dL) occurred at 60\u2009minutes with PeHI infusion vs 120\u2009minutes with PoHI and Pe406 infusion. \u0394AUC\n                      <jats:sub>epinephrine<\/jats:sub>\n                      during the 180\u2010minute insulin infusion period was two\u2010fold higher with PeHI infusion compared with PoHI and Pe406 infusion. Glucose production (mg\/kg\/min) was least suppressed with PeHI infusion (\u0394 = 0.79\u2009\u00b1\u20090.33) and equally suppressed with PoHI and Pe406 infusion (\u0394 = 1.16\u2009\u00b1\u20090.21 and 1.18\u2009\u00b1\u20090.17, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      = NS). Peak glucose utilization (mg\/kg\/min) was highest with PeHI infusion (4.94\u2009\u00b1\u20090.17) and less with PoHI and Pe406 infusion (3.58\u2009\u00b1\u20090.58 and 3.26\u2009\u00b1\u20090.08, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05 vs Pe for both).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Peripheral infusion of hepatopreferential insulin can achieve a metabolic profile that closely mimics portal insulin delivery, which reduces the risk of hypoglycaemia compared with peripheral insulin infusion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13808","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T02:18:39Z","timestamp":1560219519000},"page":"2294-2304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Peripherally delivered hepatopreferential insulin analog insulin\u2010406 mimics the hypoglycaemia\u2010sparing effect of portal vein human insulin infusion in dogs"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-0062","authenticated-orcid":false,"given":"Justin M.","family":"Gregory","sequence":"first","affiliation":[{"name":"Ian Burr Division of Pediatric Endocrinology and Diabetes Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie F.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doss W.","family":"Neal","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Farmer","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta S.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon R.","family":"Hastings","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Madsen","sequence":"additional","affiliation":[{"name":"Global Research Technologies Novo Nordisk A\/S  Maaleov Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Global Research Technologies Novo Nordisk A\/S  Maaleov Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Hostrup","sequence":"additional","affiliation":[{"name":"Global Research Technologies Novo Nordisk A\/S  Maaleov 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