We report the characterization of a new insulinotropic compound, 4-hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 μmol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans. The stimulating effect of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated the insulin secretion induced by supranormal (6.6–16.7 mmol/l) concentrations of glucose. In addition, in the isolated perfused rat pancreas, we could show 1) that the pattern of insulin secretion induced by 4-hydroxyisoleucine was biphasic, 2) that this effect occurred in the absence of any change in pancreatic α-and δ-cell activity, and 3) that the more glucose concentration was increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine did not interact with other agonists of insulin secretion (leucine, arginine, tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine insulinotropic activity might, at least in part, account for fenugreek seeds' antidiabetic properties. This secretagogue may be considered as a novel drug with potential interest for the treatment of NIDDM.
4-Hydroxyisoleucine: A Novel Amino Acid Potentiator of Insulin Secretion
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Yves Sauvaire, Pierre Petit, Christophe Broca, Michèle Manteghetti, Yves Baissac, Josepha Fernandez-Alvarez, Renè Gross, Michèle Roye, Agnès Leconte, Ramon Gomis, Gèrard Ribes; 4-Hydroxyisoleucine: A Novel Amino Acid Potentiator of Insulin Secretion. Diabetes 1 February 1998; 47 (2): 206–210. https://doi.org/10.2337/diab.47.2.206
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