Plasma Amino Acid Levels and Insulin Secretion in Obesity

Felig, Philip; Marliss, Errol B.; Cahill, George F.

doi:10.1056/nejm196910092811503

Cited by 739 publications

(489 citation statements)

References 30 publications

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“…Early studies also have shown that plasma concentrations of amino acids, particularly branched-chain amino acids, are elevated in obese insulin-resistant subjects (13,42,43). Similar to our observation in L6 myocytes, increased amino acid availability in humans during physiological hyperinsulinemia impairs glucose uptake in skeletal muscle (31).…”

Section: Discussionsupporting

confidence: 87%

Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance

Tremblay

Brûlé

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

409

329

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Section: Discussionsupporting

confidence: 87%

Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance

Tremblay

Brûlé

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

409

329

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“…However, the physiological relevance of the concentrations of BCAA and times of exposure used in the present study remain to be established. Thus, the pro‐oxidant and inflammatory effects of BCAA were observed at concentrations that could be reached in MSUD7, 27 or in daily BCAA supplementation in sportsmen,5, 6 but higher than those found in patients suffering from obesity or diabetes 8, 9. However, it is important to highlight that lower concentrations of BCAA (0.5‐2 mmol/L) already increased vascular contraction which might add physiological relevance.…”

Section: Discussionmentioning

confidence: 87%

“…Increased BCAA plasma concentrations have been found in several pathological conditions such as Maple syrup urine disease (MSUD)7 and type 2 diabetes (T2DM) and obesity 8, 9, 10. Importantly, highly elevated BCAA blood concentrations in MSUD patients are responsible for neurological damage,11 and in T2DM and obesity, elevated BCAA blood concentrations are associated with insulin resistance10, 12 and were suggested as important predictors of future diabetes and positively associated with enhanced cardiovascular risk 13, 14.…”

Section: Introductionmentioning

confidence: 99%

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Zhenyukh

González‐Amor

Rodrigues-Díez

et al. 2018

J Cellular Molecular Medi

112

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Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA‐induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.

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“…These studies have highlighted the impact of amino acids on the actions of insulin and consequently glucose metabolism. In the 1940s, Luetscher (1942) already reported higher amino acid levels among diabetic patients, and this finding was later confirmed by the demonstration of the positive correlation between amino acid levels and insulin (Felig et al 1969). Furthermore, the i.v.…”

Section: Patient Investigationsmentioning

confidence: 80%

Metabolomics in diabetes research

Friedrich¹

2012

Journal of Endocrinology

125

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Diabetes represents one of the most important global health problems because it is associated with a large economic burden on the health systems of many countries. Whereas the diagnosis and treatment of manifest diabetes have been well investigated, the identification of novel pathways or early biomarkers indicative of metabolic alterations or insulin resistance related to the development of diabetes is still in progress. Over half of the type 2 diabetes patients show manifestations of diabetes-related diseases, which highlight the need for early screening markers of diabetes. During the last decade, the rapidly growing research field of metabolomics has introduced new insights into the pathology of diabetes as well as methods to predict disease onset and has revealed new biomarkers. Recent epidemiological studies first used metabolism to predict incident diabetes and revealed branched-chain and aromatic amino acids including isoleucine, leucine, valine, tyrosine and phenylalanine as highly significant predictors of future diabetes. This review summarises the current findings of metabolic research regarding diabetes in animal models and human investigations.

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Plasma Amino Acid Levels and Insulin Secretion in Obesity

Cited by 739 publications

References 30 publications

Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance

Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Metabolomics in diabetes research

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