Acute and long‐term administration of palmitoylcarnitine induces muscle‐specific insulin resistance in mice. (31st July 2017)

• Record Type: Journal Article
• 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
• Is Part Of: BioFactors. Volume 43:Number 5(2017:Sep./Oct.)
• Page Start: 718
• Page End: 730
• Publication Date: 2017-07-31
• Subjects: acylcarnitine -- insulin resistance -- insulin release -- fatty acid metabolism -- glucose metabolism -- isopropyl‐GBB; Vitamins -- Physiological effect -- Periodicals; Trace elements -- Physiological effect -- Periodicals; Growth factors -- Physiological effect -- Periodicals; Plant growth promoting substances -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Nutritional Physiological Phenomena -- Periodicals; Trace Elements -- metabolism -- Periodicals; Vitamins -- metabolism -- Periodicals; Molecular Biology -- Periodicals; 612.399
• DOI: 10.1002/biof.1378
• Languages: English
• ISSNs: 0951-6433

Abstract

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. © 2017 BioFactors, 43(5):718–730, 2017