| Receptor isoform selective insulin analogues give tissue preferential effects. | |
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MedLine Citation:
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PMID: 21851336 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The relative expression patterns of the two insulin receptor isoforms, +/- exon11 (IR-B/A respectively), are tissue dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms, to test whether tissue-preferential biological effects can be attained. In rats and mice, IR-B is the most prominent isoform in liver (<95%) and fat (<90%), whereas in muscles IR-A is the dominant isoform (<95%). As a consequence, insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency (compared to human insulin, HI) for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared to HI) for inducing glycogen accumulation (75%) and lipogenesis (130%) than for affecting muscle (45%). For the same blood glucose lowering effect upon acute i.v. dosing to mice, INS-B gave a significantly higher degree of IR phosphorylation in liver than HI. These in vitro and in vivo results indicate that insulin analogues with IR isoform-preferential binding affinity are able to elicit tissue-selective biological responses, depending on the IR-A/B expression. |
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Authors:
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Sara Gry Vienberg; Stephan D Bouman; Heidi Sørensen; Carsten E Stidsen; Thomas Kjeldsen; Tine Glendorf; Anders Sørensen; Grith S Olsen; Birgitte Andersen; Erica Nishimura |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-18 |
Journal Detail:
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Title: The Biochemical journal Volume: - ISSN: 1470-8728 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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