Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs
In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels—occurring as the result of glucose infusion or f...
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| Veröffentlicht in: | Basic & clinical pharmacology & toxicology 2021-06, Vol.128 (6), p.783-794 |
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| creator | Gradel, Anna Katrina Jógvansdóttir Kildegaard, Jonas Porsgaard, Trine Lykkesfeldt, Jens Refsgaard, Hanne Hoffman Frølund |
| description | In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels—occurring as the result of glucose infusion or food intake—could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P |
| doi_str_mv | 10.1111/bcpt.13574 |
| format | Article |
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Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels—occurring as the result of glucose infusion or food intake—could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P < 0.05). Furthermore, higher c‐peptide but also glucagon levels were observed in fed compared to fasted pigs (P < 0.05). The pharmacokinetic profile of insulin aspart did not differ between pigs clamped at 4 vs. 10 mmol/L glucose. Hence, food intake rather than blood glucose levels within normal range modulates the pharmacokinetic properties of insulin aspart upon subcutaneous and intravenous administration in pigs.</description><identifier>ISSN: 1742-7835</identifier><identifier>EISSN: 1742-7843</identifier><identifier>DOI: 10.1111/bcpt.13574</identifier><identifier>PMID: 33626236</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Absorption ; Blood flow ; Blood glucose ; Domestic animals ; Food ; Food intake ; Glucagon ; Glucose ; Insulin ; Insulin absorption ; insulin clearance ; insulin pharmacokinetics ; Intravenous administration ; Pharmacokinetics ; Pharmacology ; subcutaneous ; variability</subject><ispartof>Basic & clinical pharmacology & toxicology, 2021-06, Vol.128 (6), p.783-794</ispartof><rights>2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd</rights><rights>2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3574-ba46167224551d5e22e31c0d98891e8ec787173b775fa356ab7249458ff3e9fc3</citedby><cites>FETCH-LOGICAL-c3574-ba46167224551d5e22e31c0d98891e8ec787173b775fa356ab7249458ff3e9fc3</cites><orcidid>0000-0001-8977-865X ; 0000-0001-5982-8417 ; 0000-0002-6514-8407 ; 0000-0002-4996-4084 ; 0000-0003-0946-5587</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbcpt.13574$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbcpt.13574$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33626236$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gradel, Anna Katrina Jógvansdóttir</creatorcontrib><creatorcontrib>Kildegaard, Jonas</creatorcontrib><creatorcontrib>Porsgaard, Trine</creatorcontrib><creatorcontrib>Lykkesfeldt, Jens</creatorcontrib><creatorcontrib>Refsgaard, Hanne Hoffman Frølund</creatorcontrib><title>Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs</title><title>Basic & clinical pharmacology & toxicology</title><addtitle>Basic Clin Pharmacol Toxicol</addtitle><description>In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels—occurring as the result of glucose infusion or food intake—could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P < 0.05). Furthermore, higher c‐peptide but also glucagon levels were observed in fed compared to fasted pigs (P < 0.05). The pharmacokinetic profile of insulin aspart did not differ between pigs clamped at 4 vs. 10 mmol/L glucose. Hence, food intake rather than blood glucose levels within normal range modulates the pharmacokinetic properties of insulin aspart upon subcutaneous and intravenous administration in pigs.</description><subject>Absorption</subject><subject>Blood flow</subject><subject>Blood glucose</subject><subject>Domestic animals</subject><subject>Food</subject><subject>Food intake</subject><subject>Glucagon</subject><subject>Glucose</subject><subject>Insulin</subject><subject>Insulin absorption</subject><subject>insulin clearance</subject><subject>insulin pharmacokinetics</subject><subject>Intravenous administration</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>subcutaneous</subject><subject>variability</subject><issn>1742-7835</issn><issn>1742-7843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE9PwyAcQInRuDm9-AEMiTeTzvKvtEddnJos0cM8N5T-2Lp1bYVWs28vtXNHuQDh5QEPoWsSTokf95lu2ilhQvITNCaS00DGnJ0e10yM0IVzmzCkkpPwHI0Yi2hEWTRGm3ld57ioWrUFbFW7BovbtapwVvYHq7LTtQNcwheUDitjQLfOE4CbtbI7pettUUFbaNzY2hQl4Np4nevKosLKNcq2foubYuUu0ZlRpYOrwzxBH_On5ewlWLw9v84eFoHuvxBkikckkpRyIUgugFJgRId5EscJgRi0jCWRLJNSGMVEpDJJecJFbAyDxGg2QbeD17_oswPXppu6s5W_MqWC8pCFsaSeuhsobWvnLJi0scVO2X1KwrTPmvZZ09-sHr45KLtsB_kR_evoATIA3z7B_h9V-jh7Xw7SH71jgqg</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Gradel, Anna Katrina Jógvansdóttir</creator><creator>Kildegaard, Jonas</creator><creator>Porsgaard, Trine</creator><creator>Lykkesfeldt, Jens</creator><creator>Refsgaard, Hanne Hoffman Frølund</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><orcidid>https://orcid.org/0000-0001-8977-865X</orcidid><orcidid>https://orcid.org/0000-0001-5982-8417</orcidid><orcidid>https://orcid.org/0000-0002-6514-8407</orcidid><orcidid>https://orcid.org/0000-0002-4996-4084</orcidid><orcidid>https://orcid.org/0000-0003-0946-5587</orcidid></search><sort><creationdate>202106</creationdate><title>Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs</title><author>Gradel, Anna Katrina Jógvansdóttir ; Kildegaard, Jonas ; Porsgaard, Trine ; Lykkesfeldt, Jens ; Refsgaard, Hanne Hoffman Frølund</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3574-ba46167224551d5e22e31c0d98891e8ec787173b775fa356ab7249458ff3e9fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Absorption</topic><topic>Blood flow</topic><topic>Blood glucose</topic><topic>Domestic animals</topic><topic>Food</topic><topic>Food intake</topic><topic>Glucagon</topic><topic>Glucose</topic><topic>Insulin</topic><topic>Insulin absorption</topic><topic>insulin clearance</topic><topic>insulin pharmacokinetics</topic><topic>Intravenous administration</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>subcutaneous</topic><topic>variability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gradel, Anna Katrina Jógvansdóttir</creatorcontrib><creatorcontrib>Kildegaard, Jonas</creatorcontrib><creatorcontrib>Porsgaard, Trine</creatorcontrib><creatorcontrib>Lykkesfeldt, Jens</creatorcontrib><creatorcontrib>Refsgaard, Hanne Hoffman Frølund</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Basic & clinical pharmacology & toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gradel, Anna Katrina Jógvansdóttir</au><au>Kildegaard, Jonas</au><au>Porsgaard, Trine</au><au>Lykkesfeldt, Jens</au><au>Refsgaard, Hanne Hoffman Frølund</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs</atitle><jtitle>Basic & clinical pharmacology & toxicology</jtitle><addtitle>Basic Clin Pharmacol Toxicol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>128</volume><issue>6</issue><spage>783</spage><epage>794</epage><pages>783-794</pages><issn>1742-7835</issn><eissn>1742-7843</eissn><abstract>In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels—occurring as the result of glucose infusion or food intake—could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P < 0.05). Furthermore, higher c‐peptide but also glucagon levels were observed in fed compared to fasted pigs (P < 0.05). The pharmacokinetic profile of insulin aspart did not differ between pigs clamped at 4 vs. 10 mmol/L glucose. Hence, food intake rather than blood glucose levels within normal range modulates the pharmacokinetic properties of insulin aspart upon subcutaneous and intravenous administration in pigs.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33626236</pmid><doi>10.1111/bcpt.13574</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8977-865X</orcidid><orcidid>https://orcid.org/0000-0001-5982-8417</orcidid><orcidid>https://orcid.org/0000-0002-6514-8407</orcidid><orcidid>https://orcid.org/0000-0002-4996-4084</orcidid><orcidid>https://orcid.org/0000-0003-0946-5587</orcidid></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Absorption Blood flow Blood glucose Domestic animals Food Food intake Glucagon Glucose Insulin Insulin absorption insulin clearance insulin pharmacokinetics Intravenous administration Pharmacokinetics Pharmacology subcutaneous variability |
| title | Food intake rather than blood glucose levels affects the pharmacokinetic profile of insulin aspart in pigs |
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