Please use this identifier to cite or link to this item:
10.1002/biof.1378
Title: | Acute and long-term administration of palmitoylcarnitine induces muscle-specific insulin resistance in mice |
Authors: | Liepinsh, Edgars Makrecka-Kuka, Marina Makarova, Elina Volska, Kristine Vilks, Karlis Sevostjanovs, Eduards Antone, Unigunde Kuka, Janis Vilskersts, Reinis Lola, Daina Loza, Einars Grinberga, Solveiga Dambrova, Maija Faculty of Pharmacy |
Keywords: | acylcarnitine;fatty acid metabolism;glucose metabolism;insulin release;insulin resistance;isopropyl-GBB;1.6 Biological sciences;3.1 Basic medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;Biochemistry;Molecular Medicine;Clinical Biochemistry |
Issue Date: | 1-Sep-2017 |
Citation: | Liepinsh , E , Makrecka-Kuka , M , Makarova , E , Volska , K , Vilks , K , Sevostjanovs , E , Antone , U , Kuka , J , Vilskersts , R , Lola , D , Loza , E , Grinberga , S & Dambrova , M 2017 , ' Acute and long-term administration of palmitoylcarnitine induces muscle-specific insulin resistance in mice ' , BioFactors , vol. 43 , no. 5 , pp. 718-730 . https://doi.org/10.1002/biof.1378 |
Abstract: | Acylcarnitine accumulation has been linked to perturbations in energy metabolism pathways. In this study, we demonstrate that long-chain (LC) acylcarnitines are active metabolites involved in the regulation of glucose metabolism in vivo. Single-dose administration of palmitoylcarnitine (PC) in fed mice induced marked insulin insensitivity, decreased glucose uptake in muscles, and elevated blood glucose levels. Increase in the content of LC acylcarnitine induced insulin resistance by impairing Akt phosphorylation at Ser473. The long-term administration of PC using slow-release osmotic minipumps induced marked hyperinsulinemia, insulin resistance, and glucose intolerance, suggesting that the permanent accumulation of LC acylcarnitines can accelerate the progression of insulin resistance. The decrease of acylcarnitine content significantly improved glucose tolerance in a mouse model of diet-induced glucose intolerance. In conclusion, we show that the physiological increase in content of acylcarnitines ensures the transition from a fed to fasted state in order to limit glucose metabolism in the fasted state. In the fed state, the inability of insulin to inhibit LC acylcarnitine production induces disturbances in glucose uptake and metabolism. The reduction of acylcarnitine content could be an effective strategy to improve insulin sensitivity. |
Description: | Publisher Copyright: © 2017 The Authors BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology |
DOI: | 10.1002/biof.1378 |
ISSN: | 0951-6433 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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Acute_and_long_term_administration.pdf | 1.2 MB | Adobe PDF | View/Open |
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