1. 4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties.
- Author
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Broca C, Gross R, Petit P, Sauvaire Y, Manteghetti M, Tournier M, Masiello P, Gomis R, and Ribes G
- Subjects
- Acids pharmacology, Animals, Diabetes Mellitus, Type 2 chemically induced, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 physiopathology, Glucose Tolerance Test, Insulin Secretion, Islets of Langerhans drug effects, Islets of Langerhans metabolism, Isoleucine chemistry, Isoleucine drug effects, Isoleucine therapeutic use, Male, Niacinamide, Rats, Rats, Wistar, Reference Values, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents therapeutic use, Insulin metabolism, Isoleucine analogs & derivatives
- Abstract
We have recently shown in vitro that 4-hydroxyisoleucine (4-OH-Ile), an amino acid extracted from fenugreek seeds, potentiates insulin secretion in a glucose-dependent manner. The present study was designed to investigate whether 4-OH-Ile could exert in vivo insulinotropic and antidiabetic properties. For this purpose, intravenous or oral glucose tolerance tests (IVGTTs and OGTTs, respectively) were performed not only in normal animals but also in a type II diabetes rat model. During IVGTT in normal rats or OGTT in normal dogs, 4-OH-Ile (18 mg/kg) improved glucose tolerance. The lactonic form of 4-OH-Ile was ineffective in normal rats. In non-insulin-dependent diabetic (NIDD) rats, a single intravenous administration of 4-OH-Ile (50 mg/kg) partially restored glucose-induced insulin response without affecting glucose tolerance; a 6-day subchronic administration of 4-OH-Ile (50 mg/kg, daily) reduced basal hyperglycemia, decreased basal insulinemia, and slightly, but significantly, improved glucose tolerance. In vitro, 4-OH-Ile (200 microM) potentiated glucose (16.7 mM)-induced insulin release from NIDD rat-isolated islets. So, the antidiabetic effects of 4-OH-Ile on NIDD rats result, at least in part, from a direct pancreatic B cell stimulation.
- Published
- 1999
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