An amino acid mixture improves glucose tolerance and insulin signaling in Sprague-Dawley rats

Abstract

The aims of this investigation were to evaluate the effect of an amino acid supplement on the glucose response to an oral glucose challenge ( experiment 1) and to evaluate whether differences in blood glucose response were associated with increased skeletal muscle glucose uptake ( experimental 2). Experiment 1 rats were gavaged with either glucose (CHO), glucose plus an amino acid mixture (CHO-AA-1), glucose plus an amino acid mixture with increased leucine concentration (CHO-AA-2), or water (PLA). CHO-AA-1 and CHO-AA-2 had reduced blood glucose responses compared with CHO, with no difference in insulin among these treatments. Experiment 2 rats were gavaged with either CHO or CHO-AA-1. Fifteen minutes after gavage, a bolus containing 2-[3H]deoxyglucose and [U-14C]mannitol was infused via a tail vein. Blood glucose was significantly lower in CHO-AA-1 than in CHO, whereas insulin responses were similar. Muscle glucose uptake was higher in CHO-AA-1 compared with CHO in both fast-twitch red (8.36 ± 1.3 vs. 5.27 ± 0.7 μmol·g−1·h−1) and white muscle (1.85 ± 0.3 vs. 1.11 ± 0.2 μmol·g−1·h−1). There was no difference in Akt/PKB phosphorylation between treatment groups; however, the amino acid treatment resulted in increased AS160 phosphorylation in both muscle fiber types. Glycogen synthase phosphorylation was reduced in fast-twitch red muscle of CHO-AA-1 compared with CHO, whereas mTOR phosphorylation was increased. These differences were not noted in fast-twitch white muscle. These findings suggest that amino acid supplementation can improve glucose tolerance by increasing skeletal muscle glucose uptake and intracellular disposal through enhanced intracellular signaling.

Insulin-Sensitizing Effect of LXR Agonist T0901317 in High-Fat Fed Rats is Associated with Restored Muscle GLUT4 Expression and Insulin-Stimulated AS160 Phosphorylation

“…Surprisingly, enhanced phosphorylation of AS160 upon LXR activation, that was found in our study, was not associated with improved Akt/PKB phosphorylation. Similar observation for rat skeletal muscle was reported also in the study by Bernard et al [24] where insulin sensitivity was enhanced by amino acid supplementation. We can only speculate as to the mechanism of LXR-induced improvement in muscle insulin-stimulated AS160 phosphorylation.…”

Leucine Stimulates Insulin Secretion via Down-regulation of Surface Expression of Adrenergic α2A Receptor through the mTOR (Mammalian Target of Rapamycin) Pathway

“…Glucose tolerance was found to be compromised in animals fed a low protein diet (1,2). Besides its possible effect on glucose uptake by skeletal muscle (2,3), a low protein diet has been found to directly impair pancreatic secretion of insulin in response to glucose (1,4). Conversely, ingestion of proteins or amino acids together with carbohydrates leads to strong insulin secretion in humans and animal models (2,3,5).…”

“…Besides its possible effect on glucose uptake by skeletal muscle (2,3), a low protein diet has been found to directly impair pancreatic secretion of insulin in response to glucose (1,4). Conversely, ingestion of proteins or amino acids together with carbohydrates leads to strong insulin secretion in humans and animal models (2,3,5). Leucine is one of the most potent insulin secretagogues among the branchedchain amino acids that facilitates glucose-induced insulin release from pancreatic ␤-cells (6).…”

“…The mammalian target of rapamycin (mTOR) 3 pathway has recently emerged as a critical regulator of cellular metabolism in response to growth factors and nutrients (13,14). Leucine is a potent stimulator of mTOR.…”

Essential Amino Acid Supplementation for the Prevention and Treatment of Obesity

“…In particular, improved glucose metabolism was observed following long-term dietary supplementation with leucine in mice maintained on a high-fat diet [142] or in the presence of an elevated EAA:non-EAA ratio with no change in dietary carbohydrate and fat content [143]. Indeed, oral administration of a BCAA-enriched mixture and high glucose improved glucose tolerance in comparison with unsupplemented rats [144]. This result was confirmed in elderly rodents following prolonged supplementation with a BCAA-enriched mixture; their basal level of IRS-1 serine-636 phosphorylation appeared to be unchanged [123].…”