Stimulus‐secretion coupling of arginine‐induced insulin release: Significance of changes in extracellular and intracellular pH

Malaisse, Willy; Plasman, Pierre-Olivier; Blachier, François; Herchuelz, André; Sener, Abdullah

doi:10.1002/cbf.290090102

Cited by 16 publications

(10 citation statements)

References 24 publications

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“…In addition, an increase in plasma insulin concentration has been reported following the intravenous infusion of free amino acids in both healthy (7)(8)(9) and type 2 diabetic subjects (10). In accordance, various in vitro studies using incubated ␤-cells of the pancreas have described strong insulinotropic effects of arginine, leucine, and phenylalanine (11)(12)(13)(14)(15)(16)(17)(18). Recently, we performed a series of studies in which we determined the in vivo insulinotropic potential of various free amino acids and protein (hydrolysates) when ingested in combination with carbohydrates in healthy young subjects (19 -21).…”

mentioning

confidence: 66%

“…Substantial progress has recently been made in the understanding of the mechanisms and signaling pathways by which leucine (12,(15)(16)(17), arginine (13)(14)(15)(16)30), and phenylalanine and its derivatives (18) stimulate ␤-cell function and insulin secretion in in vitro studies using isolated ␤-cells and insulinsecreting pancreatic ␤-cell lines. Clearly, the large responsiveness to the coingestion of the insulinotropic amino acid/protein mixture in the present study strongly suggests that amino acids can provide a glucose-independent stimulus to the pancreatic ␤-cells that is preserved in patients with long-term type 2 diabetes.…”

Section: Figure 2-plasma Glucose Concentration (A) and Response (B) Omentioning

confidence: 99%

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Amino Acid Ingestion Strongly Enhances Insulin Secretion in Patients With Long-Term Type 2 Diabetes

et al. 2003

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OBJECTIVE -Insulin secretion in response to carbohydrate intake is blunted in type 2 diabetic patients. However, it is not clear whether the insulin response to other stimuli, such as amino acids, is also diminished. Recently, we defined an optimal insulinoptropic mixture containing free leucine, phenylalanine, and a protein hydrolysate that substantially enhances the insulin response in healthy young subjects when coingested with carbohydrate. In this study, we aimed to investigate the insulinotropic capacity of this mixture in long-term type 2 diabetic patients.RESEARCH DESIGN AND METHODS -Ten type 2 diabetic patients (aged 59.1 Ϯ 2.0 years, BMI 26.5 Ϯ 0.7 kg/m 2 ) and 10 healthy control subjects (58.8 Ϯ 2.1 years, 26.5 Ϯ 0.7 kg/m 2 ) visited our lab twice, during which insulin responses were determined following ingestion of carbohydrate only (CHO) or carbohydrate with the free amino acid/protein mixture (CHOϩPRO). All subjects received 0.7 g ⅐ kg Ϫ1 ⅐ h Ϫ1 carbohydrate with or without 0.35 g ⅐ kg Ϫ1⅐ h Ϫ1 of the amino acid/protein mixture.RESULTS -Insulin responses were dramatically increased in the CHOϩPRO trial in both the type 2 diabetic and control groups (189 and 114%, respectively) compared with the CHO trial (P Ͻ 0.01). Plasma glucose, glucagon, growth hormone, cortisol, IGF-I, and IGF binding protein 3 responses were not different between trials within the 2-h time frame.CONCLUSIONS -The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal. Diabetes Care 26:625-630, 2003

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confidence: 66%

Section: Figure 2-plasma Glucose Concentration (A) and Response (B) Omentioning

confidence: 99%

Amino Acid Ingestion Strongly Enhances Insulin Secretion in Patients With Long-Term Type 2 Diabetes

et al. 2003

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“…transport (Collarini & Oxender 1987) and subsequent action on the cell. Although many studies have been performed to elucidate the mechanism of L-arginine-and L-leucine-induced insulin secretion (Henquin & Meissner 1981, Charles & Henquin 1983, Hermans et al 1987, Blachier et al 1989, Grapengeisser et al 1989, Malaisse et al 1991, the effects of many other amino acids including L-alanine, -aminoisobutyric acid and glycine are poorly understood, while others including L-proline and L-serine have been neglected.…”

Section: Discussionmentioning

confidence: 98%

Mechanisms of amino acid-induced insulin secretion from the glucose-responsive BRIN-BD11 pancreatic B-cell line

McClenaghan¹,

Barnett²,

O’Harte³

et al. 1996

Journal of Endocrinology

105

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The effects of different classes of amino acids known to be transported and utilized by pancreatic B-cells were examined using the novel glucose-responsive pancreatic B-cell line, BRIN-BD11. Amino acids tested included alpha-aminoisobutyric acid, L-alanine, L-arginine, L-glutamine, glycine, L-leucine, L-lysine, L-proline and L-serine. At non-stimulatory (1.1 mmol/l) glucose, acute incubations with either 1 or 10 mmol/l amino acid evoked 1.3- to 4.7-fold increases of insulin release. Raising glucose to 16.7 mmol/l enhanced the effects of all amino acids except L-glutamine, and increased insulin output at 10 mmol/l compared with 1 mmol/l amino acid. Glyceraldehyde (10 mmol/l) also served to promote 10 mmol/l amino acid-induced insulin secretion with the exceptions of L-arginine, glycine, L-lysine and L-proline. At 16.7 mmol/l glucose, diazoxide (300 mumol/l) significantly decreased the secretory response to all amino acids except L-glutamine. Likewise, verapamil (20 mumol/l) or depletion of extracellular Ca2+ reduced insulin output indicating the importance of Ca2+ influx in the actions of amino acids. These data indicate that BRIN-BD11 cells transport and utilize amino acids, acting in association with glycolysis, K(+)-ATP channels and/or voltage-dependent Ca2+ channels to promote Ca2+ influx and insulin secretion. The response of BRIN-BD11 cells to glucose and amino acids indicates that this is a useful cell line for future research on the mechanisms of nutrient regulation of insulin secretion.

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“…Four free amino acids (leucine, phenylalanine, arginine, and glutamine) were tested. Several in vitro studies showed that these amino acids have a strong stimulating effect on insulin release by pancreatic ␤-cells (12)(13)(14)19). Floyd et al (5,7) observed that 30 g arginine injected intravenously in vivo in human subjects led to an equal insulin response as occurred with the mixture of 10 amino acids (30 g in total; arginine, lysine, phenylalanine, leucine, valine, methionine, histidine, isoleucine, threonine, and tryptophan).…”

Section: Discussionmentioning

confidence: 99%

Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate

Loon

Saris

Verhagen

et al. 2000

The American Journal of Clinical Nutrition

318

220

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Background: Protein induces an increase in insulin concentrations when ingested in combination with carbohydrate. Increases in plasma insulin concentrations have been observed after the infusion of free amino acids. However, the insulinotropic properties of different amino acids or protein (hydrolysates) when coingested with carbohydrate have not been investigated. Objective: The aim of this study was to define an amino acid and protein (hydrolysate) mixture with a maximal insulinotropic effect when co-ingested with carbohydrate. Design: Eight healthy, nonobese male subjects visited our laboratory, after an overnight fast, on 10 occasions on which different beverage compositions were tested for 2 h. During those trials the subjects ingested 0.8 g · kg Ϫ1 · h Ϫ1 carbohydrate and 0.4 g · kg Ϫ1 ·h Ϫ1 of an amino acid and protein (hydrolysate) mixture. Results: A strong initial increase in plasma glucose and insulin concentrations was observed in all trials, after which large differences in insulin response between drinks became apparent. After we expressed the insulin response as area under the curve during the second hour, ingestion of the drinks containing free leucine, phenylalanine, and arginine and the drinks with free leucine, phenylalanine, and wheat protein hydrolysate were followed by the largest insulin response (101% and 103% greater, respectively, than with the carbohydrate-only drink; P < 0.05). Conclusions: Insulin responses are positively correlated with plasma leucine, phenylalanine, and tyrosine concentrations. A mixture of wheat protein hydrolysate, free leucine, phenylalanine, and carbohydrate can be applied as a nutritional supplement to strongly elevate insulin concentrations.Am J Clin Nutr 2000;72:96-105. KEY WORDSInsulin secretion, amino acid supplementation, protein hydrolysates, leucine, arginine, phenylalanine, glutamine, healthy men INTRODUCTIONThe synergistically stimulating effect of the combined intake of carbohydrates and protein on plasma insulin concentrations was described for the first time in the 1960s (1, 2) and was confirmed later by Nuttall et al (3,4). The insulinotropic effect of intravenous amino acid administration was also studied in the 1960s by . Infusion of several amino acids led to significant increases in plasma insulin. A mixture of 10 amino acids and equimolar quantities of arginine or leucine only were found to be the most potentiating. Floyd et al also observed a synergistic effect when glucose was administered intravenously with these amino acids. After different combinations of amino acids were investigated, the combined intravenous administration of arginine-leucine and arginine-phenylalanine, together with glucose, resulted in the largest increase in plasma insulin concentrations. Several in vitro studies using incubated ␤-cells of the pancreas showed strong insulinotropic effects of arginine, leucine, phenylalanine, and leucine in combination with glutamine (11)(12)(13)(14)(15)(16)(17)(18)(19)(20).A strong elevation of plasma insulin concentrations ...

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Stimulus‐secretion coupling of arginine‐induced insulin release: Significance of changes in extracellular and intracellular pH

Cited by 16 publications

References 24 publications

Amino Acid Ingestion Strongly Enhances Insulin Secretion in Patients With Long-Term Type 2 Diabetes

Amino Acid Ingestion Strongly Enhances Insulin Secretion in Patients With Long-Term Type 2 Diabetes

Mechanisms of amino acid-induced insulin secretion from the glucose-responsive BRIN-BD11 pancreatic B-cell line

Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate

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