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Peripherally delivered hepatopreferential insulin analog insulin‐406 mimics the hypoglycaemia‐sparing effect of portal vein human insulin infusion in dogs
Aims We previously quantified the hypoglycaemia‐sparing 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‐406, could similarly protect against hypoglycae...
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| Published in: | Diabetes, obesity & metabolism obesity & metabolism, 2019-10, Vol.21 (10), p.2294-2304 |
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| creator | Gregory, Justin M. Kraft, Guillaume Scott, Melanie F. Neal, Doss W. Farmer, Ben Smith, Marta S. Hastings, Jon R. Madsen, Peter Kjeldsen, Thomas B. Hostrup, Susanne Brand, Christian L. Fledelius, Christian Nishimura, Erica Cherrington, Alan D. |
| description | Aims
We previously quantified the hypoglycaemia‐sparing 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‐406, could similarly protect against hypoglycaemia.
Materials and methods
Dogs received human insulin infusions into either the hepatic portal vein (PoHI, n = 7) or a peripheral vein (PeHI, n = 7) for 180 minutes at four‐fold the basal secretion rate (6.6 pmol/kg/min) in a previous study. Insulin‐406 (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 minutes. Glucagon was fixed at basal concentrations, mimicking the diminished α‐cell response seen in type 1 diabetes.
Results
Glucose dropped quickly with PeHI infusion, reaching 41 ± 3 mg/dL at 60 minutes, but more slowly with PoHI and Pe406 infusion (67 ± 2 and 72 ± 4 mg/dL, respectively; P |
| doi_str_mv | 10.1111/dom.13808 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8132115</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2254502838</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4438-25f350e6152a5809bc5576579304833a5917a42b8717f09838b2d747ddd88f913</originalsourceid><addsrcrecordid>eNp1kUtu1TAUhiMEoqUwYAPIEhMYpPUjjp0JUlWeUlEZwNjyjU8SV44d7OSizFgCK2BxrATf3vYKkPDEPvKnz8fnL4qnBJ-SvM5MGE8Jk1jeK45JVbOSMFrfvznTUjaYHhWPUrrGGFdMiofFESNEsobVx8XPTxDtNEDUzq3IgLNbiGDQAJOewxShy6WfrXbI-rQ465H22oX-rvz1_UeFazTa0bYJzQOgYZ1C79ZWw2h1vk6Tjtb3CLoO2hmFDk0hzlm4hWwbllH7g9v6bkk27A7IhD49Lh502iV4crufFF_evvl88b68vHr34eL8smyr_KWS8o5xDDXhVHOJm03Luai5aBiuJGOaN0Toim6kIKLDjWRyQ42ohDFGyq4h7KR4tfdOy2YE0-Yv54moKdpRx1UFbdXfN94Oqg9bJfOoCeFZ8OJWEMPXBdKsRptacE57CEtSlPKKY5pfzujzf9DrsMQ81B0lBa04Z3WmXu6pNoaUcg6HZghWu9RVTl3dpJ7ZZ392fyDvYs7A2R74Zh2s_zep11cf98rfZz27jg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2287245536</pqid></control><display><type>article</type><title>Peripherally delivered hepatopreferential insulin analog insulin‐406 mimics the hypoglycaemia‐sparing effect of portal vein human insulin infusion in dogs</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Gregory, Justin M. ; Kraft, Guillaume ; Scott, Melanie F. ; Neal, Doss W. ; Farmer, Ben ; Smith, Marta S. ; Hastings, Jon R. ; Madsen, Peter ; Kjeldsen, Thomas B. ; Hostrup, Susanne ; Brand, Christian L. ; Fledelius, Christian ; Nishimura, Erica ; Cherrington, Alan D.</creator><creatorcontrib>Gregory, Justin M. ; Kraft, Guillaume ; Scott, Melanie F. ; Neal, Doss W. ; Farmer, Ben ; Smith, Marta S. ; Hastings, Jon R. ; Madsen, Peter ; Kjeldsen, Thomas B. ; Hostrup, Susanne ; Brand, Christian L. ; Fledelius, Christian ; Nishimura, Erica ; Cherrington, Alan D.</creatorcontrib><description>Aims
We previously quantified the hypoglycaemia‐sparing 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‐406, could similarly protect against hypoglycaemia.
Materials and methods
Dogs received human insulin infusions into either the hepatic portal vein (PoHI, n = 7) or a peripheral vein (PeHI, n = 7) for 180 minutes at four‐fold the basal secretion rate (6.6 pmol/kg/min) in a previous study. Insulin‐406 (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 minutes. Glucagon was fixed at basal concentrations, mimicking the diminished α‐cell response seen in type 1 diabetes.
Results
Glucose dropped quickly with PeHI infusion, reaching 41 ± 3 mg/dL at 60 minutes, but more slowly with PoHI and Pe406 infusion (67 ± 2 and 72 ± 4 mg/dL, respectively; P < 0.01 vs PeHI for both). The hypoglycaemic nadir (c. 40 mg/dL) occurred at 60 minutes with PeHI infusion vs 120 minutes with PoHI and Pe406 infusion. ΔAUCepinephrine during the 180‐minute insulin infusion period was two‐fold higher with PeHI infusion compared with PoHI and Pe406 infusion. Glucose production (mg/kg/min) was least suppressed with PeHI infusion (Δ = 0.79 ± 0.33) and equally suppressed with PoHI and Pe406 infusion (Δ = 1.16 ± 0.21 and 1.18 ± 0.17, respectively; P = NS). Peak glucose utilization (mg/kg/min) was highest with PeHI infusion (4.94 ± 0.17) and less with PoHI and Pe406 infusion (3.58 ± 0.58 and 3.26 ± 0.08, respectively; P < 0.05 vs Pe for both).
Conclusions
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.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.13808</identifier><identifier>PMID: 31183936</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Blood Glucose - analysis ; Blood Glucose - metabolism ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Type 1 ; Dogs ; dynamics ; Glucagon ; Gluconeogenesis ; Glucose ; Glucose metabolism ; Humans ; hypoglycaemia ; Hypoglycemia ; Hypoglycemia - metabolism ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - pharmacology ; Infusions, Intravenous ; Insulin ; Insulin - administration & dosage ; Insulin - analogs & derivatives ; Insulin - blood ; Insulin - pharmacology ; insulin analogues ; Insulin, Regular, Human - administration & dosage ; Insulin, Regular, Human - pharmacology ; Liver ; Liver - metabolism ; Male ; Mimicry ; Portal vein ; Portal Vein - metabolism ; Secretion ; type 1 diabetes</subject><ispartof>Diabetes, obesity & metabolism, 2019-10, Vol.21 (10), p.2294-2304</ispartof><rights>2019 John Wiley & Sons Ltd</rights><rights>2019 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4438-25f350e6152a5809bc5576579304833a5917a42b8717f09838b2d747ddd88f913</citedby><cites>FETCH-LOGICAL-c4438-25f350e6152a5809bc5576579304833a5917a42b8717f09838b2d747ddd88f913</cites><orcidid>0000-0003-2700-0062</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31183936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gregory, Justin M.</creatorcontrib><creatorcontrib>Kraft, Guillaume</creatorcontrib><creatorcontrib>Scott, Melanie F.</creatorcontrib><creatorcontrib>Neal, Doss W.</creatorcontrib><creatorcontrib>Farmer, Ben</creatorcontrib><creatorcontrib>Smith, Marta S.</creatorcontrib><creatorcontrib>Hastings, Jon R.</creatorcontrib><creatorcontrib>Madsen, Peter</creatorcontrib><creatorcontrib>Kjeldsen, Thomas B.</creatorcontrib><creatorcontrib>Hostrup, Susanne</creatorcontrib><creatorcontrib>Brand, Christian L.</creatorcontrib><creatorcontrib>Fledelius, Christian</creatorcontrib><creatorcontrib>Nishimura, Erica</creatorcontrib><creatorcontrib>Cherrington, Alan D.</creatorcontrib><title>Peripherally delivered hepatopreferential insulin analog insulin‐406 mimics the hypoglycaemia‐sparing effect of portal vein human insulin infusion in dogs</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aims
We previously quantified the hypoglycaemia‐sparing 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‐406, could similarly protect against hypoglycaemia.
Materials and methods
Dogs received human insulin infusions into either the hepatic portal vein (PoHI, n = 7) or a peripheral vein (PeHI, n = 7) for 180 minutes at four‐fold the basal secretion rate (6.6 pmol/kg/min) in a previous study. Insulin‐406 (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 minutes. Glucagon was fixed at basal concentrations, mimicking the diminished α‐cell response seen in type 1 diabetes.
Results
Glucose dropped quickly with PeHI infusion, reaching 41 ± 3 mg/dL at 60 minutes, but more slowly with PoHI and Pe406 infusion (67 ± 2 and 72 ± 4 mg/dL, respectively; P < 0.01 vs PeHI for both). The hypoglycaemic nadir (c. 40 mg/dL) occurred at 60 minutes with PeHI infusion vs 120 minutes with PoHI and Pe406 infusion. ΔAUCepinephrine during the 180‐minute insulin infusion period was two‐fold higher with PeHI infusion compared with PoHI and Pe406 infusion. Glucose production (mg/kg/min) was least suppressed with PeHI infusion (Δ = 0.79 ± 0.33) and equally suppressed with PoHI and Pe406 infusion (Δ = 1.16 ± 0.21 and 1.18 ± 0.17, respectively; P = NS). Peak glucose utilization (mg/kg/min) was highest with PeHI infusion (4.94 ± 0.17) and less with PoHI and Pe406 infusion (3.58 ± 0.58 and 3.26 ± 0.08, respectively; P < 0.05 vs Pe for both).
Conclusions
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.</description><subject>Animals</subject><subject>Blood Glucose - analysis</subject><subject>Blood Glucose - metabolism</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes Mellitus, Type 1</subject><subject>Dogs</subject><subject>dynamics</subject><subject>Glucagon</subject><subject>Gluconeogenesis</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Humans</subject><subject>hypoglycaemia</subject><subject>Hypoglycemia</subject><subject>Hypoglycemia - metabolism</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Infusions, Intravenous</subject><subject>Insulin</subject><subject>Insulin - administration & dosage</subject><subject>Insulin - analogs & derivatives</subject><subject>Insulin - blood</subject><subject>Insulin - pharmacology</subject><subject>insulin analogues</subject><subject>Insulin, Regular, Human - administration & dosage</subject><subject>Insulin, Regular, Human - pharmacology</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mimicry</subject><subject>Portal vein</subject><subject>Portal Vein - metabolism</subject><subject>Secretion</subject><subject>type 1 diabetes</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kUtu1TAUhiMEoqUwYAPIEhMYpPUjjp0JUlWeUlEZwNjyjU8SV44d7OSizFgCK2BxrATf3vYKkPDEPvKnz8fnL4qnBJ-SvM5MGE8Jk1jeK45JVbOSMFrfvznTUjaYHhWPUrrGGFdMiofFESNEsobVx8XPTxDtNEDUzq3IgLNbiGDQAJOewxShy6WfrXbI-rQ465H22oX-rvz1_UeFazTa0bYJzQOgYZ1C79ZWw2h1vk6Tjtb3CLoO2hmFDk0hzlm4hWwbllH7g9v6bkk27A7IhD49Lh502iV4crufFF_evvl88b68vHr34eL8smyr_KWS8o5xDDXhVHOJm03Luai5aBiuJGOaN0Toim6kIKLDjWRyQ42ohDFGyq4h7KR4tfdOy2YE0-Yv54moKdpRx1UFbdXfN94Oqg9bJfOoCeFZ8OJWEMPXBdKsRptacE57CEtSlPKKY5pfzujzf9DrsMQ81B0lBa04Z3WmXu6pNoaUcg6HZghWu9RVTl3dpJ7ZZ392fyDvYs7A2R74Zh2s_zep11cf98rfZz27jg</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Gregory, Justin M.</creator><creator>Kraft, Guillaume</creator><creator>Scott, Melanie F.</creator><creator>Neal, Doss W.</creator><creator>Farmer, Ben</creator><creator>Smith, Marta S.</creator><creator>Hastings, Jon R.</creator><creator>Madsen, Peter</creator><creator>Kjeldsen, Thomas B.</creator><creator>Hostrup, Susanne</creator><creator>Brand, Christian L.</creator><creator>Fledelius, Christian</creator><creator>Nishimura, Erica</creator><creator>Cherrington, Alan D.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2700-0062</orcidid></search><sort><creationdate>201910</creationdate><title>Peripherally delivered hepatopreferential insulin analog insulin‐406 mimics the hypoglycaemia‐sparing effect of portal vein human insulin infusion in dogs</title><author>Gregory, Justin M. ; Kraft, Guillaume ; Scott, Melanie F. ; Neal, Doss W. ; Farmer, Ben ; Smith, Marta S. ; Hastings, Jon R. ; Madsen, Peter ; Kjeldsen, Thomas B. ; Hostrup, Susanne ; Brand, Christian L. ; Fledelius, Christian ; Nishimura, Erica ; Cherrington, Alan D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4438-25f350e6152a5809bc5576579304833a5917a42b8717f09838b2d747ddd88f913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Blood Glucose - analysis</topic><topic>Blood Glucose - metabolism</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes Mellitus, Type 1</topic><topic>Dogs</topic><topic>dynamics</topic><topic>Glucagon</topic><topic>Gluconeogenesis</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>Humans</topic><topic>hypoglycaemia</topic><topic>Hypoglycemia</topic><topic>Hypoglycemia - metabolism</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Infusions, Intravenous</topic><topic>Insulin</topic><topic>Insulin - administration & dosage</topic><topic>Insulin - analogs & derivatives</topic><topic>Insulin - blood</topic><topic>Insulin - pharmacology</topic><topic>insulin analogues</topic><topic>Insulin, Regular, Human - administration & dosage</topic><topic>Insulin, Regular, Human - pharmacology</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mimicry</topic><topic>Portal vein</topic><topic>Portal Vein - metabolism</topic><topic>Secretion</topic><topic>type 1 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gregory, Justin M.</creatorcontrib><creatorcontrib>Kraft, Guillaume</creatorcontrib><creatorcontrib>Scott, Melanie F.</creatorcontrib><creatorcontrib>Neal, Doss W.</creatorcontrib><creatorcontrib>Farmer, Ben</creatorcontrib><creatorcontrib>Smith, Marta S.</creatorcontrib><creatorcontrib>Hastings, Jon R.</creatorcontrib><creatorcontrib>Madsen, Peter</creatorcontrib><creatorcontrib>Kjeldsen, Thomas B.</creatorcontrib><creatorcontrib>Hostrup, Susanne</creatorcontrib><creatorcontrib>Brand, Christian L.</creatorcontrib><creatorcontrib>Fledelius, Christian</creatorcontrib><creatorcontrib>Nishimura, Erica</creatorcontrib><creatorcontrib>Cherrington, Alan D.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gregory, Justin M.</au><au>Kraft, Guillaume</au><au>Scott, Melanie F.</au><au>Neal, Doss W.</au><au>Farmer, Ben</au><au>Smith, Marta S.</au><au>Hastings, Jon R.</au><au>Madsen, Peter</au><au>Kjeldsen, Thomas B.</au><au>Hostrup, Susanne</au><au>Brand, Christian L.</au><au>Fledelius, Christian</au><au>Nishimura, Erica</au><au>Cherrington, Alan D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peripherally delivered hepatopreferential insulin analog insulin‐406 mimics the hypoglycaemia‐sparing effect of portal vein human insulin infusion in dogs</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2019-10</date><risdate>2019</risdate><volume>21</volume><issue>10</issue><spage>2294</spage><epage>2304</epage><pages>2294-2304</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aims
We previously quantified the hypoglycaemia‐sparing 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‐406, could similarly protect against hypoglycaemia.
Materials and methods
Dogs received human insulin infusions into either the hepatic portal vein (PoHI, n = 7) or a peripheral vein (PeHI, n = 7) for 180 minutes at four‐fold the basal secretion rate (6.6 pmol/kg/min) in a previous study. Insulin‐406 (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 minutes. Glucagon was fixed at basal concentrations, mimicking the diminished α‐cell response seen in type 1 diabetes.
Results
Glucose dropped quickly with PeHI infusion, reaching 41 ± 3 mg/dL at 60 minutes, but more slowly with PoHI and Pe406 infusion (67 ± 2 and 72 ± 4 mg/dL, respectively; P < 0.01 vs PeHI for both). The hypoglycaemic nadir (c. 40 mg/dL) occurred at 60 minutes with PeHI infusion vs 120 minutes with PoHI and Pe406 infusion. ΔAUCepinephrine during the 180‐minute insulin infusion period was two‐fold higher with PeHI infusion compared with PoHI and Pe406 infusion. Glucose production (mg/kg/min) was least suppressed with PeHI infusion (Δ = 0.79 ± 0.33) and equally suppressed with PoHI and Pe406 infusion (Δ = 1.16 ± 0.21 and 1.18 ± 0.17, respectively; P = NS). Peak glucose utilization (mg/kg/min) was highest with PeHI infusion (4.94 ± 0.17) and less with PoHI and Pe406 infusion (3.58 ± 0.58 and 3.26 ± 0.08, respectively; P < 0.05 vs Pe for both).
Conclusions
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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>31183936</pmid><doi>10.1111/dom.13808</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2700-0062</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Animals Blood Glucose - analysis Blood Glucose - metabolism Diabetes Diabetes mellitus Diabetes mellitus (insulin dependent) Diabetes Mellitus, Type 1 Dogs dynamics Glucagon Gluconeogenesis Glucose Glucose metabolism Humans hypoglycaemia Hypoglycemia Hypoglycemia - metabolism Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - pharmacology Infusions, Intravenous Insulin Insulin - administration & dosage Insulin - analogs & derivatives Insulin - blood Insulin - pharmacology insulin analogues Insulin, Regular, Human - administration & dosage Insulin, Regular, Human - pharmacology Liver Liver - metabolism Male Mimicry Portal vein Portal Vein - metabolism Secretion type 1 diabetes |
| title | Peripherally delivered hepatopreferential insulin analog insulin‐406 mimics the hypoglycaemia‐sparing effect of portal vein human insulin infusion in dogs |
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