Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose

SummaryInterest in the effect of proteins or amino acids on glucose metabolism dates back at least a century, largely because it was demonstrated that the amino acids from ingested protein could be converted into glucose. Indeed, these observations influenced the dietary information provided to people with diabetes. Subsequently it was shown that ingested protein did not raise the blood glucose concentration. It also was shown that proteins could stimulate a rise in insulin and glucagon but the response to various proteins was different. In addition, it was shown that individual amino acids also could stimulate a rise in insulin and in glucagon concentrations. When individual amino acids are ingested by normal subjects, there is an ordering of the insulin and glucagon responses. However, the order is not the same for insulin and glucagon. In addition, the metabolic response cannot be predicted based on the functional groups of the amino acids. Thus, empirical prediction of the metabolic response to ingested single amino acids is not possible. IUBMBIUBMB Life, 62(9): [660][661][662][663][664][665][666][667][668] 2010

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“…4). This occurred even though the increase in that specific amino acid also was attenuated when ingested with glucose (17,26,30,31).…”

Section: Effect Of Ingestion Of Individual Amino Acids With Glucosementioning

confidence: 98%

“…The results for several of the amino acids have been published, that is, arginine (26), glycine (27), proline (17), phenylalanine (28), isoleucine (29), leucine (30), and lysine (31).…”

Section: Our Personal Observationsmentioning

confidence: 99%

Amino acid ingestion and glucose metabolism—A review

2010

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“…Sugars are well known for stimulating insulin secretion, and similarly, certain AAs (e.g., leucine, arginine) are also potent insulin secretagogues (21,23), with EAA-mediated postprandial secretion of insulin amplified by sugars (19). Crucially, insulin itself modulates microvascular blood flow via nitric oxide (NO)-dependent vasodilation of precapillary arterioles (29,43).…”

Section: Metabolic Homeostasismentioning

confidence: 99%

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

Phillips

Atherton

Varadhan

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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-Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 Ϯ 2.1 yr) under postabsorptive and fed [iv Glamin (ϳ10 g AA), glucose ϳ7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-13 C2] leucine and [ 2 H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (ϩ12 Ϯ 5%, P Ͻ 0.05), MBV (ϩ25 Ϯ 10%, P Ͻ 0.05), and MPS (ϩ129 Ϯ 33%, P Ͻ 0.05) increased. Infusion of methacholine further enhanced LBF (ϩ126 Ϯ 12%, P Ͻ 0.05) and MBV (ϩ79 Ϯ 30%, P Ͻ 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 Ϯ 0.004 vs. 0.08 Ϯ 0.01%/h, P Ͻ 0.05) nor improvements in NPB (Ϫ4.4 Ϯ 2.4 vs. 16.4 Ϯ 5.7 nmol Phe·100 ml leg Ϫ1 ·min Ϫ1 , P Ͻ 0.05) were affected by methacholine infusion (MPS 0.07 Ϯ 0.01%/h; NPB 24.0 Ϯ 7.7 nmol Phe·100 ml leg Ϫ1 ·min Ϫ1 ), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism. blood flow; protein metabolism; muscle SKELETAL MUSCLES SERVE CRUCIAL locomotory and postprandial metabolic [e.g., amino acid (AA) and glucose disposal] functions (52). Given such vital functions, understanding the control of nutrient delivery in the context of muscle metabolism is important. The day-to-day stability of muscle mass in healthy, habitually active individuals (not engaged in formal exercise training) is the result of a dynamic equilibrium in muscle protein turnover, whereby rates of muscle protein synthesis (MPS) are balanced with those of breakdown (MPB) (4, 27). This equilibrium depends on the postprandial supply of essential amino acid (EAA) components of dietary protein, which provide the substrate and "signal" to recoup postabsorptive muscle protein losses. This role of EAAs has been delineated in both human (8, 32, 36) and animal work (1, 2, 15).Before EAA can act either as substrates or signals for MPS, they must leave the bloodstream, transverse the interstitial fluid, and be transported into myocytes (12). Potentially, then, both delivery and transendothelial AA transport could be rate limiting for the uptake of circulating AA by muscle ...

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“…Leucine and its transaminated product a-ketoisocaproate may also affect insulin secretion via direct inhibition of b-cell ATP-regulated potassium channel currents . Correspondingly, acute in vivo studies consistently revealed that additional leucine intake increased insulin secretion and reduced postprandial blood glucose (Kalogeropoulou et al 2008). However, there are conflicting results on the longterm effects of leucine on b-cell function.…”

Section: Introductionmentioning

confidence: 99%

Chronic exposure to leucine in vitro induces β-cell dysfunction in INS-1E cells and mouse islets

Liu

Jeppesen

Gregersen

et al. 2012

Journal of Endocrinology

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Chronic hyperglycemia and hyperlipidemia cause deleterious effects on b-cell function. Interestingly, increased circulating amino acid (AA) levels are also a characteristic of the prediabetic and diabetic state. The chronic effects of AAs on b-cell function remain to be determined. Isolated mouse islets and INS-1E cells were incubated with or without excess leucine. After 72 h, leucine increased basal insulin secretion and impaired glucose-stimulated insulin secretion in both mouse islets and INS-1E cells, corroborating the existence of aminoacidotoxicity-induced b-cell dysfunction. This took place concomitantly with alterations in proteins and genes involved in insulin granule transport, trafficking (e.g. collapsin response mediator protein 2 and GTP-binding nuclear protein Ran), insulin signal transduction (proteasome subunit a type 6), and the oxidative phosphorylation pathway (cytochrome c oxidase). Leucine downregulated insulin 1 gene expression but upregulated pancreas duodenum homeobox 1 and insulin 2 mRNA expressions. Importantly, cholesterol (CH) accumulated in INS-1E cells concomitantly with upregulation of enzymes involved in CH biosynthesis (e.g. 3-hydroxy-3-methylglutaryl-CoA reductase, mevalonate (diphospho) decarboxylase, and squalene epoxidase) and LDL receptor, whereas triglyceride content was decreased. Our findings indicate that chronic exposure to elevated levels of leucine may have detrimental effects on both b-cell function and insulin sensitivity. Aminoacidotoxicity may play a pathogenic role in the development of type 2 diabetes.

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Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose

Cited by 98 publications

References 19 publications

Amino acid ingestion and glucose metabolism—A review

Amino acid ingestion and glucose metabolism—A review

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

Chronic exposure to leucine in vitro induces β-cell dysfunction in INS-1E cells and mouse islets

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