title: 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion.
abstract: 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 micromol/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 alpha- and delta-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.
authors.affiliation: Laboratoire de Recherche sur les Substances Naturelles Végétales, Université Montpellier II, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Sauvaire
authors.forename: P
authors.initials: P
authors.lastname: Petit
authors.forename: C
authors.initials: C
authors.lastname: Broca
authors.forename: M
authors.initials: M
authors.lastname: Manteghetti
authors.forename: Y
authors.initials: Y
authors.lastname: Baissac
authors.forename: J
authors.initials: J
authors.lastname: Fernandez-Alvarez
authors.forename: R
authors.initials: R
authors.lastname: Gross
authors.forename: M
authors.initials: M
authors.lastname: Roye
authors.forename: A
authors.initials: A
authors.lastname: Leconte
authors.forename: R
authors.initials: R
authors.lastname: Gomis
authors.forename: G
authors.initials: G
authors.lastname: Ribes
mesh_terms: D000818:Animals; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007532:Isoleucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010936:Plant Extracts / Q000737:chemistry*; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D029910:Trigonella
chemical_list: C104672:4-hydroxyisoleucine; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D007532:Isoleucine; C056164:fenugreek seed meal; D005947:Glucose