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Arginine, leucine, or histidine, and glucose were each administered intravenously, in 30-gm. amounts on separate occasions to the same healthy subjects. Each of the amino acids and glucose in these same amounts were administered also as mixtures. Synergism in the stimulation of the release of insulin was demonstrated when the sum of the increases in plasma insulin which resulted from the separate administrations of an amino acid and glucose was exceeded by that obtained when they were administered as a mixture. A synergistic effect was exerted by each of the three amino acid-glucose combinations; it was greatest with arginine and glucose and least with histidine and glucose. Synergism probably results from the effects of these stimuli upon the pancreatic beta cell; it is not dependent upon humoral gastrointestinal factors released after the ingestion of these nutrients. DIABETES 19: 109-15, February, 1970. We have reported that the intravenous administration of individual amino acids, as well as of mixtures of amino acids, induces the release of insulin. 2 " 5 In the course of these studies it was demonstrated that the elevations in blood glucose observed during the infusion of some amino acids cannot be the major cause of the insulin release, which was observed. Although there was not a good correlation between increases in blood glucose and increases in plasma insulin, some of the infusions of individual amino acids and mixtures of amino acids which were accompanied by the larger and more consistent increases in blood glucose were also the more potent in stimulating the release of insulin. This suggested that the insulin-releasing effect of certain amino acids might be potentiated by the concomitant elevations of blood glucose.The present studies were undertaken to determine if certain amino acids might act synergistically with glucose to effect the release of insulin. Three essential amino acids (arginine, leucine, and histidine) and glucose were each administered intravenously in 30-gm. amounts on separate occasions to the same healthy subjects. Glucose and each of the amino acids in the same amounts were • administered also as mixtures. The results demonstrate that a synergistic effect upon the release of insulin is exerted by arginine and glucose, leucine and glucose; and histidine and glucose. 1 The effect was greatest with glucose and arginine and least with glucose and histidine. The synergistic effect appears to result from an action of these stimuli upon the pancreatic beta cell and is not dependent upon humoral, gastrointestinal or other known factors released after the ingestion of these nutrients. MATERIAL AND METHODSEight healthy, nonobese* males, aged twenty to twenty-nine (mean 23.5) years, served as subjects. These active subjects maintained their habitual ad libitum food intake but took no food during the nine hours before they were given the infusions.L-arginine, 1-leucine, 1-histidine, and d-glucose were infused individually in 30-gm. amounts over periods of thirty minutes. Thirty grams of...

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