Insulin resistance and the metabolism of branched-chain amino acids in humans

Abstract

Peripheral resistance to insulin action is the major mechanism causing the metabolic syndrome and eventually type 2 diabetes mellitus. The metabolic derangement associated with insulin resistance is extensive and not restricted to carbohydrates. The branched-chain amino acids (BCAAs) are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in conditions featuring insulin resistance, insulin deficiency, or both. Obesity, the metabolic syndrome and diabetes mellitus display a gradual increase in the plasma concentration of BCAAs, from the obesity-related low-grade insulin-resistant state to the severe deficiency of insulin action in diabetes ketoacidosis. Obesity-associated hyperinsulinemia succeeds in maintaining near-normal or slightly elevated plasma concentration of BCAAs, despite the insulin-resistant state. The low circulating levels of insulin and/or the deeper insulin resistance occurring in diabetes mellitus are associated with more marked elevation in the plasma concentration of BCAAs. In diabetes ketoacidosis, the increase in plasma BCAAs is striking, returning to normal when adequate metabolic control is achieved. The metabolism of BCAAs is also disturbed in other situations typically featuring insulin resistance, including kidney and liver dysfunction. However, notwithstanding the insulin-resistant state, the plasma level of BCAAs in these conditions is lower than in healthy subjects, suggesting that these organs are involved in maintaining BCAAs blood concentration. The pathogenesis of the decreased BCAAs plasma level in kidney and liver dysfunction is unclear, but a decreased afflux of these amino acids into the blood stream has been observed.

Effect of branched‑chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients

“…At present, the role of BCAAs and their implications in the development of IR remain controversial. Indeed, in obese or overweight individuals, BCAAs have been reported to induce IR (49).…”

Branched-chain amino acids alter neurobehavioral function in rats

“…Recent studies have revealed that a cluster of metabolites comprised of the branched-chain amino acids (BCAA) leucine (Leu), isoleucine (Ile), and valine (Val) and their metabolites, as well as the aromatic amino acids (AAA) tyrosine (Tyr) and phenylalanine (Phe), are strongly associated with obesity and insulin resistance in humans (1,10,29,43,67,78). Moreover, a very similar metabolite cluster predicts incident type 2 diabetes in longitudinal studies in humans (64) and, when measured at baseline in obese subjects, also predicts improvement in insulin sensitivity in response to a dietary/behavioral weight loss intervention (63).…”

Plasma levels of various amino acids and their changes upon protein uptakes in Japanese young and old men and women

“…Thus it is quite natural that plasma levels of BCAAs increase in patients of type 2 diabetes [4][5][6][7] because the metabolism of such amino acids are impaired.…”

“…Branched-chain amino acids concentrations have been shown to be elevated in response to overnutrition and can affect insulin sensitivity and secretion [3]. Number of human studies have consistently indicated that concentrations of BCAAs in plasma and urine are associated with insulin resistance [4][5][6][7]. We recently examined relationship between various foods uptakes and body mass index (BMI) and various plasma parameters in Japanese young and old men and women [8].…”