4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion.
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.
Sauvaire
Y
Y
Laboratoire de Recherche sur les Substances Naturelles Végétales, Université Montpellier II, France.
Petit
P
P
Broca
C
C
Manteghetti
M
M
Baissac
Y
Y
Fernandez-Alvarez
J
J
Gross
R
R
Roye
M
M
Leconte
A
A
Gomis
R
R
Ribes
G
G
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
C104672:4-hydroxyisoleucine; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D007532:Isoleucine; C056164:fenugreek seed meal; D005947:Glucose