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L-leucine stimulation of glucose uptake and utilization involves modulation of glucose – lipid metabolic switch and improved bioenergetic homeostasis in isolated rat psoas muscle ex vivo

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Abstract

The antidiabetic effect of l-leucine has been attributed to its modulatory effect on glucose uptake and lipid metabolism in muscles. However, there is a dearth on its effect on glucose metabolism in muscles. Thus, the present study investigated the effect of l-leucine – stimulated glucose uptake on glucose metabolism, dysregulated lipid metabolic pathways, redox and bioenergetic homeostasis, and proteolysis in isolated psoas muscle from Sprague Dawley male rats. Isolated psoas muscles were incubated with l-leucine (30–240 μg/mL) in the presence of 11.1 mMol glucose at 37 ˚C for 2 h. Muscles incubated in only glucose served as the control, while muscles not incubated in l-leucine and/or glucose served as the normal control. Metformin (6.04 mM) was used as the standard antidiabetic drug. Incubation with l-leucine caused a significant increase in muscle glucose uptake, with an elevation of glutathione levels, superoxide dismutase, catalase, E-NTPDase and 5’nucleotidase activities. It also led to the depletion of malondialdehyde and nitric oxide levels, ATPase, chymotrypsin, acetylcholinesterase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and lipase activities. There was an alteration in lipid metabolites, with concomitant activation of glycerolipid metabolism, fatty acid metabolism, and fatty acid elongation in mitochondria in the glucose-incubated muscle (negative control). Incubation with l-leucine reversed these alterations, and concomitantly deactivated the pathways. These results indicate that l-leucine-enhanced muscle glucose uptake involves improved redox and bioenergetic homeostasis, with concomitant suppressed proteolytic, glycogenolytic and gluconeogenetic activities, while modulating glucose – lipid metabolic switch.

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Authors and Affiliations

  1. Department of Pharmacology, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, 9301, South Africa

    Ochuko L. Erukainure

  2. Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa

    Veronica F. Salau

  3. Department of Chemistry, University of Ilorin, Ilorin, Nigeria

    Olubunmi Atolani

  4. DiSTABiF, University of Campania “Luigi Vanvitelli”, Via Vivaldi 43, 81100, Caserta, Italy

    Rahul Ravichandran

  5. Institute for Physiology, Charité – University Medicine Berlin, Berlin, Germany

    Priyanka Banerjee & Robert Preissner

  6. School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa

    Neil A. Koorbanally & Md. Shahidul Islam

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  1. Ochuko L. Erukainure
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  2. Veronica F. Salau
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Erukainure, O.L., Salau, V.F., Atolani, O. et al. L-leucine stimulation of glucose uptake and utilization involves modulation of glucose – lipid metabolic switch and improved bioenergetic homeostasis in isolated rat psoas muscle ex vivo. Amino Acids 53, 1135–1151 (2021). https://doi.org/10.1007/s00726-021-03021-8

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