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Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog
Endogenous insulin secretion exposes the liver to three times higher insulin concentrations than the rest of the body. Because subcutaneous insulin delivery eliminates this gradient and is associated with metabolic abnormalities, functionally restoring the physiologic gradient may provide therapeuti...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392933/ https://www.ncbi.nlm.nih.gov/pubmed/24947349 http://dx.doi.org/10.2337/db14-0266 |
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author | Edgerton, Dale S. Moore, Mary C. Winnick, Jason J. Scott, Melanie Farmer, Ben Naver, Helle Jeppesen, Claus B. Madsen, Peter Kjeldsen, Thomas B. Nishimura, Erica Brand, Christian L. Cherrington, Alan D. |
author_facet | Edgerton, Dale S. Moore, Mary C. Winnick, Jason J. Scott, Melanie Farmer, Ben Naver, Helle Jeppesen, Claus B. Madsen, Peter Kjeldsen, Thomas B. Nishimura, Erica Brand, Christian L. Cherrington, Alan D. |
author_sort | Edgerton, Dale S. |
collection | PubMed |
description | Endogenous insulin secretion exposes the liver to three times higher insulin concentrations than the rest of the body. Because subcutaneous insulin delivery eliminates this gradient and is associated with metabolic abnormalities, functionally restoring the physiologic gradient may provide therapeutic benefits. The effects of recombinant human insulin (HI) delivered intraportally or peripherally were compared with an acylated insulin model compound (insulin-327) in dogs. During somatostatin and basal portal vein glucagon infusion, insulin was infused portally (PoHI; 1.8 pmol/kg/min; n = 7) or peripherally (PeHI; 1.8 pmol/kg/min; n = 8) and insulin-327 (Pe327; 7.2 pmol/kg/min; n = 5) was infused peripherally. Euglycemia was maintained by glucose infusion. While the effects on liver glucose metabolism were greatest in the PoHI and Pe327 groups, nonhepatic glucose uptake increased most in the PeHI group. Suppression of lipolysis was greater during PeHI than PoHI and was delayed in Pe327 infusion. Thus small increments in portal vein insulin have major consequences on the liver, with little effect on nonhepatic glucose metabolism, whereas insulin delivered peripherally cannot act on the liver without also affecting nonhepatic tissues. Pe327 functionally restored the physiologic portal–arterial gradient and thereby produced hepato-preferential effects. |
format | Online Article Text |
id | pubmed-4392933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-43929332015-11-01 Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog Edgerton, Dale S. Moore, Mary C. Winnick, Jason J. Scott, Melanie Farmer, Ben Naver, Helle Jeppesen, Claus B. Madsen, Peter Kjeldsen, Thomas B. Nishimura, Erica Brand, Christian L. Cherrington, Alan D. Diabetes Pharmacology and Therapeutics Endogenous insulin secretion exposes the liver to three times higher insulin concentrations than the rest of the body. Because subcutaneous insulin delivery eliminates this gradient and is associated with metabolic abnormalities, functionally restoring the physiologic gradient may provide therapeutic benefits. The effects of recombinant human insulin (HI) delivered intraportally or peripherally were compared with an acylated insulin model compound (insulin-327) in dogs. During somatostatin and basal portal vein glucagon infusion, insulin was infused portally (PoHI; 1.8 pmol/kg/min; n = 7) or peripherally (PeHI; 1.8 pmol/kg/min; n = 8) and insulin-327 (Pe327; 7.2 pmol/kg/min; n = 5) was infused peripherally. Euglycemia was maintained by glucose infusion. While the effects on liver glucose metabolism were greatest in the PoHI and Pe327 groups, nonhepatic glucose uptake increased most in the PeHI group. Suppression of lipolysis was greater during PeHI than PoHI and was delayed in Pe327 infusion. Thus small increments in portal vein insulin have major consequences on the liver, with little effect on nonhepatic glucose metabolism, whereas insulin delivered peripherally cannot act on the liver without also affecting nonhepatic tissues. Pe327 functionally restored the physiologic portal–arterial gradient and thereby produced hepato-preferential effects. American Diabetes Association 2014-11 2014-10-13 /pmc/articles/PMC4392933/ /pubmed/24947349 http://dx.doi.org/10.2337/db14-0266 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
spellingShingle | Pharmacology and Therapeutics Edgerton, Dale S. Moore, Mary C. Winnick, Jason J. Scott, Melanie Farmer, Ben Naver, Helle Jeppesen, Claus B. Madsen, Peter Kjeldsen, Thomas B. Nishimura, Erica Brand, Christian L. Cherrington, Alan D. Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog |
title | Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog |
title_full | Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog |
title_fullStr | Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog |
title_full_unstemmed | Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog |
title_short | Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog |
title_sort | changes in glucose and fat metabolism in response to the administration of a hepato-preferential insulin analog |
topic | Pharmacology and Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392933/ https://www.ncbi.nlm.nih.gov/pubmed/24947349 http://dx.doi.org/10.2337/db14-0266 |
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