Effect of metformin on bioactive lipid metabolism in insulin-resistant muscle

The Journal of Endocrinology
P ZabielskiAgnieszka Blachnio-Zabielska

Abstract

Intramuscular accumulation of bioactive lipids leads to insulin resistance and type 2 diabetes (T2D). There is lack of consensus concerning which of the lipid mediators has the greatest impact on muscle insulin action in vivo Our aim was to elucidate the effects of high-fat diet (HFD) and metformin (Met) on skeletal muscle bioactive lipid accumulation and insulin resistance (IR) in rats. We employed a [U-13C]palmitate isotope tracer and mass spectrometry to measure the content and fractional synthesis rate (FSR) of intramuscular long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). Eight weeks of HFD-induced intramuscular accumulation of LCACoA, DAG and Cer accompanied by both systemic and skeletal muscle IR. Metformin treatment improved insulin sensitivity at both systemic and muscular level by the augmentation of Akt/PKB and AS160 phosphorylation and decreased the content of DAG and Cer and their respective FSR. Principal component analysis (PCA) of lipid variables revealed that altered skeletal muscle IR was associated with lipid species containing 18-carbon acyl-chain, especially with C18:0-Cer, C18:1-Cer, 18:0/18:2-DAG and 18:2/18:2-DAG, but not palmitate-derived lipids. It is concluded that the insulin-s...Continue Reading

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Citations

Aug 2, 2018·Journal of Cellular Physiology·Piotr ZabielskiAgnieszka U Blachnio-Zabielska
Dec 14, 2018·International Journal of Molecular Sciences·Agnieszka U Blachnio-ZabielskaPiotr Zabielski
Jan 30, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alec I McKenzieMicah J Drummond
Dec 18, 2019·Journal of Clinical Medicine·Hady Razak HadyAdam J Krętowski
May 8, 2020·Nutrients·Iwona KojtaAgnieszka Błachnio-Zabielska
Aug 28, 2020·Frontiers in Endocrinology·Sophie Tan-ChenEric Hajduch
Aug 28, 2020·Frontiers in Endocrinology·Steven K Malin, Nathan R Stewart
Oct 11, 2020·International Journal of Molecular Sciences·Iwona KojtaAgnieszka Błachnio-Zabielska
Aug 4, 2019·Trends in Endocrinology and Metabolism : TEM·Sisitha U JayasingheFrancesca Amati
Nov 3, 2020·Frontiers in Endocrinology·Mika HilvoReijo Laaksonen
Feb 2, 2021·Journal of Diabetes and Metabolic Disorders·Abhijit A GhadgeAniket A Kuvalekar
Nov 2, 2021·American Journal of Physiology. Endocrinology and Metabolism·Saori KakehiHirotaka Watada

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