Insulin Regulation of Lysine and α-Aminoadipic Acid Dynamics and Amino Metabolites in Women With and Without Insulin Resistance.

Autor:	Chang AY; Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL., Asokan AK; Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN., Lalia AZ; Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN., Sakrikar D; Mayo Clinic Metabolomics Core, Mayo Clinic College of Medicine, Rochester, MN., Lanza IR; Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN.; Mayo Clinic Metabolomics Core, Mayo Clinic College of Medicine, Rochester, MN., Petterson XM; Mayo Clinic Metabolomics Core, Mayo Clinic College of Medicine, Rochester, MN., Nair KS; Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2024 Oct 01; Vol. 73 (10), pp. 1592-1604.
DOI:	10.2337/db23-0977
Abstrakt:	Insulin is a key regulator of amino acid metabolism. Many plasma amino acids, including lysine and its metabolite, α-aminoadipic acid (α-AA), a predictor for developing diabetes, are elevated in insulin resistance (IR). In 18 overweight women with IR and polycystic ovary syndrome compared with 12 lean control women, high physiological insulin during a euglycemic clamp failed to normalize many elevated amino acid metabolites, including branched-chain and aromatic amino acids, α-aminobutyric acid, and lysine, but normalized α-AA. To understand the underpinnings of differential responses of lysine and its metabolic product α-AA to high physiological insulin in IR compared with control participants, we developed a kinetic model using [α-15N1]-lysine and [13C1]-α-AA as tracers and measured the two tracers simultaneously in α-AA by innovative mass spectrometry. High insulin increased lysine conversion to α-AA in the IR and control groups but failed to normalize plasma lysine concentrations in IR due to a decrease in lysine metabolic clearance rate (MCR). In contrast, despite higher conversion rates of lysine to α-AA by high insulin, α-AA concentration decreased in IR because of the sustained greater MCR of α-AA. The abnormal amino acids and metabolites, even while on high physiological insulin, could potentially explain many functional derangements in IR. (© 2024 by the American Diabetes Association.)
Databáze:	MEDLINE
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