solo per esperti, 4-idrossiisoleucina

***Guru*** · 19-10-2003, 21:01:45

Funge, funge.
Gli studi ci sono e se domani metto a posto il pc li posto.

Bye.

**arabafenice** · 19-10-2003, 21:13:45

L'uomo degli studi è Guru io so solo che si usa per via sperimentale come agente per il trattamento del diabete di tipo 2, quindi prodotto usabile come insulino simile

Ciao
A

***Guru*** · 19-10-2003, 21:29:46

Per il momento, tiè!
4-Hydroxyisoleucine: effects of synthetic and natural analogues on insulin secretion.

Broca C, Manteghetti M, Gross R, Baissac Y, Jacob M, Petit P, Sauvaire Y, Ribes G.

UMR 9921 du Centre National de la Recherche Scientifique, Montpellier, France. broca@zeus.sc.univ-montp1.fr

4-Hydroxyisoleucine, a peculiar amino acid extracted from fenugreek seeds and never found in mammalian tissues, exhibits interesting insulinotropic activity. To investigate the structural requirements for this stimulating effect, the insulinotropic activity of the major isomer (2S,3R,4S) of 4-hydroxyisoleucine, in the presence of 8. 3 mM glucose, was compared to that of (1) its minor isomer (2R,3R, 4S) (2) its lactone form, (3) classical structurally related amino acids, and (4) synthetic monomethylated analogues. In the isolated, ex vivo, perfused rat pancreas, only the major isomer of 4-hydroxyisoleucine (200 microM) potentiated insulin release. On incubated isolated rat islets, the threshold concentration for a significant increase (P<0.05) in insulin release was 200 microM for (2S,3R,4S) 4-hydroxyisoleucine, 500 microM for (2S,4R) and (2S,4S) gamma-hydroxynorvalines as well as (2S,3S) and (2S,3R) gamma-hydroxyvalines, and 1 mM or more for other congeners. In conclusion, the insulinotropic properties of 4-hydroxyisoleucine, in the micromolar range, are seen only in the presence of the linear major isoform; they also require carbon alpha in S-configuration, full methylation and carbon gamma-hydroxylation.

Bye.

***Guru*** · 19-10-2003, 21:30:56

Ecco l'altro:

4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties.

Broca C, Gross R, Petit P, Sauvaire Y, Manteghetti M, Tournier M, Masiello P, Gomis R, Ribes G.

Unite Mixte de Recherche 9921 du Centre National de la Recherche Scientifique, Faculte de Medecine UPRES EA 1677, 34060 Montpellier, France. broca2zeus.sc.univ-montp1.fr

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.

***Guru*** · 19-10-2003, 21:31:53

E questo per capire cos'è:

4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion.

Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J, Gross R, Roye M, Leconte A, Gomis R, Ribes G.

Laboratoire de Recherche sur les Substances Naturelles Vegetales, Universite Montpellier II, France.

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.