Acute and long-term administration of palmitoylcarnitine induces muscle-specific insulin resistance in mice

Edgars Liepinsh, Marina Makrecka-Kuka, Elina Makarova, Kristine Volska, Karlis Vilks, Eduards Sevostjanovs, Unigunde Antone, Janis Kuka, Reinis Vilskersts, Daina Lola, Einars Loza, Solveiga Grinberga, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)718-730
Number of pages13
JournalBioFactors
Volume43
Issue number5
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • acylcarnitine
  • fatty acid metabolism
  • glucose metabolism
  • insulin release
  • insulin resistance
  • isopropyl-GBB

Field of Science

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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