β-alanine scavenging of free radicals protects mitochondrial function and enhances both insulin secretion and glucose uptake in cells under metabolic stress

Billacura, Merell P, Lavilla, Charlie Jr, Cripps, Michael J, Hanna, Katie, Sale, Craig ORCID: https://orcid.org/0000-0002-5816-4169 and Turner, Mark D ORCID: https://orcid.org/0000-0001-7175-1053 (2022) β-alanine scavenging of free radicals protects mitochondrial function and enhances both insulin secretion and glucose uptake in cells under metabolic stress. Advances in Redox Research, 6. 100050. ISSN 2667-1379

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Abstract

Type 2 diabetes is a disease characterized by dysregulation of glucose homeostasis, with numerous diabetic complications attributable to the resulting chronic exposure of cells and tissues to elevated concentrations of glucose and fatty acids. This in part results from formation of advanced glycation end-products and advanced lipidation end-products that can form adducts with proteins, lipids, or DNA and disrupt their normal cellular function. There is, however, growing evidence that supplementation with the endogenous histidine-containing dipeptide, carnosine, or its rate-limiting precursor, β-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and related conditions. Here we investigated the scavenging potential of β-alanine in INS-1 pancreatic β-cells and C2C12 skeletal muscle myotubes, and show a significant reduction of >60% in reactive species that were generated by glucolipotoxic metabolic stress in both cell types following incubation with β-alanine for 5 days. Furthermore, β-alanine supplementation resulted in a protective action that helped prevent the damaging action of metabolic stress that otherwise leads to inhibition of mitochondrial function in both cell types. This in turn resulted in >60% preservation of insulin secretion and glucose uptake, in INS-1 cells and C2C12 cells respectively, which would otherwise be inhibited by metabolic stress. This suggests potential therapeutic benefit to taking β-alanine supplements as an alternative to carnosine.