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Amino Acids. 2005 Feb;28(1):71-6. Epub 2004 Dec 2.
The addition of fenugreek extract (Trigonella foenum-graecum) to glucose feeding increases muscle glycogen resynthesis after exercise. Ruby BC, Gaskill SE, Slivka D, Harger SG.
Department of Health and Human Performance, The University of Montana, Missoula, Montana 59812-1825, USA.
brent.ruby@mso.umt.edu The purpose of this study was to determine the effects of ingesting an oral supplement containing 4-Hydroxyisoleucine (4-OH-Ile, isolated from fenugreek seeds [Trigonella foenum-graecum]) with a glucose beverage on rates of post-exercise muscle glycogen resynthesis in trained male cyclists. Following an overnight fast (12 hr), subjects completed a 90-minute glycogen depletion ride after which a muscle biopsy was obtained from the vastus lateralis. Immediately and 2 hours after the muscle biopsy, subjects ingested either an oral dose of dextrose (Glu) (1.8 g.kg BW(-1)) or 4-OH-Ile supplement (Glu+4-OH-Ile, including 2.0 mg.kg(-1) 4-OH-Ile with the same oral dose of dextrose) with a second muscle biopsy 4 hours after exercise. Post exercise muscle glycogen concentration was similar for both trials. Overall, there was a significant increase in glucose and insulin concentrations from time 0 throughout the majority of the 4-hour recovery period, with no significant differences between the two trials at any time point. Although muscle glycogen concentration significantly increased from immediately post exercise to 4 hr of recovery for both trials, the net rate of muscle glycogen resynthesis was 63% greater during Glu+4-OH-Ile (10.6+/-3.3 vs. 6.5+/-2.6 g.kg wet wt.(-1).hr.(-1) for the Glu+4-OH-Ile and Glu trials, respectively). These data demonstrate that when the fenugreek extract supplement (4-OH-Ile) is added to a high oral dose of dextrose, rates of post-exercise glycogen resynthesis are enhanced above dextrose alone.
PMID: 15719265 [PubMed - indexed for MEDLINE]
Biosci Biotechnol Biochem. 2005 Jun;69(6):1186-8.
Effects of fenugreek seed extract in obese mice fed a high-fat diet. Handa T, Yamaguchi K, Sono Y, Yazawa K.
Laboratory of Nutraceuticals and Functional Foods Science, Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, Konan, Tokyo, Japan.
It was found that fenugreek seed extract reduced the body weight gain induced by a high-fat diet in obese mice. The extract decreased plasma triglyceride gain induced by oil administration. The major component of the extract, 4-hydroxyisoleucine, also decreased plasma triglyceride gain. Consequently, fenugreek seed extract is expected to prevent the obesity induced by a high-fat diet.
PMID: 15973051 [PubMed - in process]
Am J Physiol. 1999 Oct;277(4 Pt 1):E617-23.
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.
Am J Physiol Endocrinol Metab. 2004 Sep;287(3):E463-71. Epub 2004 Apr 13.
Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat.
Broca C, Breil V, Cruciani-Guglielmacci C, Manteghetti M, Rouault C, Derouet M, Rizkalla S, Pau B, Petit P, Ribes G, Ktorza A, Gross R, Reach G, Taouis M.
Laboratoire de Pharmacologie, Centre de Pharmacologie et Biotechnologies pour la Sante-Unite Mixte de Recherche 5160 Centre National de la Recherche Scientifique, Faculte de Medecine, 34060 Montpellier, France.
christophe.broca@univ-montp1.fr ID-1101 (4-hydroxyisoleucine), an amino acid extracted from fenugreek seeds, exhibits an interesting glucose-dependent insulin-stimulating activity. The present study was undertaken to investigate a possible extrapancreatic effect of ID-1101 on insulin signaling and action besides its previously described insulinotropic action. Insulin-sensitizing effects of ID-1101 were investigated in rat in vivo by three different approaches: 1) using euglycemic hyperinsulinemic clamps in two different rat models of insulin resistance, i.e., Zucker fa/fa rats and rats fed a sucrose-lipid diet; 2) measuring liver and muscle phosphatidylinositol (PI) 3-kinase activity after an acute injection of ID-1101 in normal and insulin-resistant diabetic rats; and 3) after chronic treatment in two rat models of insulin resistance. Euglycemic hyperinsulinemic clamp experiments revealed that ID-1101 can improve insulin resistance through an increase of peripheral glucose utilization rate in sucrose-lipid-fed rats and by decreasing hepatic glucose production in Zucker fa/fa rats. Moreover, we demonstrated that a single injection of ID-1101 activates the PI 3-kinase activity in liver and muscle from normal rats but also in muscle from diabetic rats. Finally, chronic ID-1101 treatment significantly reduced insulinemia in type 2 diabetic rats and reduced the progression of hyperinsulinemia in insulin-resistant obese Zucker fa/fa rats. These findings clearly demonstrate that ID-1101 can reduce insulin resistance through activation of the early steps of insulin signaling in peripheral tissues and in liver. In summary, ID-1101, besides its insulinotropic effect, directly improves insulin sensitivity, making it a potentially very valuable therapeutic agent for diabetes treatment.
PMID: 15082420 [PubMed - indexed for MEDLINE]
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