Meijer, Rick I. and Barrett, Eugene J. (2021) The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney. Biomedicines, 9 (1). p. 37. ISSN 2227-9059
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Abstract
The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.
Item Type: | Article |
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Subjects: | Eurolib Press > Biological Science |
Depositing User: | Managing Editor |
Date Deposited: | 15 Feb 2023 06:16 |
Last Modified: | 22 May 2024 08:27 |
URI: | http://info.submit4journal.com/id/eprint/442 |