Carnosine increases insulin-stimulated glucose uptake and reduces methylglyoxal-modified proteins in type-2 diabetic human skeletal muscle cells

Matthews, Joseph J. and Turner, Mark D. and Santos, Livia and Elliott-Sale, Kirsty J. and Sale, Craig (2023) Carnosine increases insulin-stimulated glucose uptake and reduces methylglyoxal-modified proteins in type-2 diabetic human skeletal muscle cells. Amino Acids. ISSN 0939-4451

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Abstract

Type-2 diabetes (T2D) is characterised by a dysregulation of metabolism, including skeletal muscle insulin resistance, mitochondrial dysfunction, and oxidative stress. Reactive species, such as methylglyoxal (MGO) and 4-hydroxynonenal (4-HNE), positively associate with T2D disease severity and can directly interfere with insulin signalling and glucose uptake in skeletal muscle by modifying cellular proteins. The multifunctional dipeptide carnosine, and its rate-limiting precursor β-alanine, have recently been shown to improve glycaemic control in humans and rodents with diabetes. However, the precise mechanisms are unclear and research in human skeletal muscle is limited. Herein, we present novel findings in primary human T2D and lean healthy control (LHC) skeletal muscle cells. Cells were differentiated to myotubes, and treated with 10 mM carnosine, 10 mM β-alanine, or control for 4-days. T2D cells had reduced ATP-linked and maximal respiration compared with LHC cells (p = 0.016 and p = 0.005). Treatment with 10 mM carnosine significantly increased insulin-stimulated glucose uptake in T2D cells (p = 0.047); with no effect in LHC cells. Insulin-stimulation increased MGO-modified proteins in T2D cells by 47%; treatment with carnosine attenuated this increase to 9.7% (p = 0.011). There was no effect treatment on cell viability or expression of other proteins. These findings suggest that the beneficial effects of carnosine on glycaemic control may be explained by its scavenging actions in human skeletal muscle.

Item Type:	Article
Identification Number:	10.1007/s00726-022-03230-9
Dates:	Date Event 18 December 2022 Accepted 13 January 2023 Published Online
Uncontrolled Keywords:	diabetes, prediabetes, glycaemia, metabolism, therapeutics
Subjects:	CAH03 - biological and sport sciences > CAH03-02 - sport and exercise sciences > CAH03-02-01 - sport and exercise sciences
Divisions:	Faculty of Health, Education and Life Sciences > Centre for Life and Sport Sciences (C-LASS)
Depositing User:	Gemma Tonks
Date Deposited:	30 Jan 2023 13:39
Last Modified:	30 Jan 2023 13:40
URI:	https://www.open-access.bcu.ac.uk/id/eprint/14151

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