• 4-hydroxyisoleucine

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      What do you guys/girls think of this stuff? Could be used during Bulking since Insulin promotes transport of amino acids from the bloodstream into muscles and other cells. Insulin also increases the rate at which amino acids are incorporated into protein. Could be used with SU/UA and T3 (maybe ECA or clen) kinda mimic the actions of DNP/insulin and T3?? To help maintain gains after a cycle of androgens and losing body fat while maintaining lean body mass.



      It is an extract from Fenugreek, which EAS has made inclusion with in their new Phosphagen HP formula (“XP” or something along such lines). Purported in the presence of carbs to increase Insulin this could make a good adjunct to a post workout shake/creatine formulation.

      Doubt that many have much feedback with this compound (alone, or as used with other ingredients [which they can objectively give notice to]).



      wow …I was thisclose to asking if anyone has any data, thoughts or opinions on this stuff as well as it is fairly foreign to me…Thanks, Mike



      Perhaps this will shed some light. Haven’t read this yet myself. A couple of abstracts and the full-text of one article. Sorry about the formatting and lack of images/links–nothing I can do about that.

      Unique Identifier


      Medline Identifier



      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. [email]broca@zeus.sc.univ-montp1.fr[/email]


      4-Hydroxyisoleucine: effects of synthetic and natural analogues on insulin secretion.


      European Journal of Pharmacology. 390(3):339-45, 2000 Mar 3.


      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. ———————————————————————————————- Unique Identifier 10516120 Medline Identifier 99447236 Authors Broca C. Gross R. Petit P. Sauvaire Y. Manteghetti M. Tournier M. Masiello P. Gomis R. Ribes G. Institution 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 Title 4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties. Source American Journal of Physiology. 277(4 Pt 1):E617-23, 1999 Oct. 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. ——————————————————————————————- 4-Hydroxyisoleucine: A Novel Amino Acid Potentiator of Insulin Secretion Sauvaire, Yves; Petit, Pierre; Broca, Christophe; Manteghetti, Michele; Baissac, Yves; Fernandez-Alvarez, Josepha; Gross, Rene; Roye, Michele; Leconte, Agnes; Gomis, Ramon; Ribes, Gerard From the Laboratoire de Recherche sur les Substances Naturelles Vegetales (Y. Sauvaire, Y. Baissac), Unite Propre de Recherche Enseignement Superieur EA 1677, Universite Montpellier II; the Laboratoire de Pharmacologie (P. Petit, C. Broca, A. Leconte), Unite Propre de Recherche Enseignement Superieur EA 1677, Faculte de Medecine; the Unite Mixte de Recherche (C. Broca, M. Manteghetti, R. Gomis, M. Roye, G. Ribes), Centre National de la Recherche Scientifique, UMR 9921, Universite Montpellier I, Montpellier, France; and the Endocrinology Unit (J. Fernandez-Alvarez, R. Gomis), Hospital Clinic, Barcelona, Spain. Address correspondence and reprint requests to Yves Sauvaire, Laboratoire de Recherche sur les Substances Naturelles Vegetales, Universite Montpellier II, Place Eugene Bataillon, 34095 Montpellier Cedex 05, France. Received for publication 2 January 1997 and accepted in revised form 22 October 1997. ——————————————————————————– 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 micro mol/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. Diabetes 47:206-210, 1998 ——————————————————————————– TLC, thin-layer chromatography; HPLC, high-performance liquid chromatography; [alpha]20D, optical rotation. Beta-cell defect and insulin resistance are essential features of NIDDM [1-4], and both features are the focus of intensive investigations. In this context, plants are a source of many biochemical substances that present interesting therapeutic properties [5]. Thus from traditional medicine, the antidiabetic properties of fenugreek (Trigonella foenum-groenum L. leguminosae) seeds have been known for a long time. These properties have been evaluated in animals [6-9] and humans [10] and are generally attributed to the high-fiber content of the seeds and the subsequent reduction of intestinal glucose absorption [11]. We showed that the fiber-rich extract of fenugreek seeds from testa + endosperm was able to decrease hyperglycemia and glycosuria in insulin-dependent alloxan diabetic dogs [9]. However, more recently, we reported [12] that chronic administration of a second fenugreek seed extract obtained from cotyledons + axes increased plasma insulin levels in normal rats. From this second extract, which was found to contain many water-soluble substances, including steroid saponins, trigonelline, flavonoids, and free amino acids, we have isolated and purified 4-hydroxyisoleucine, which is the most typical amino acid in this genus. This substance appeared to be a novel insulinotropic compound when tested in three different preparations, particularly human pancreatic islets. RESEARCH DESIGN AND METHODS Isolation and identification of 4-hydroxyisoleucine. Fenugreek seeds (cultivar Gouka) were obtained from our experimental field at the Montpellier II University, Montpellier, France. Mature seeds were ground and defatted with hexane using a Soxhlet apparatus, and the powder (100 g) was extracted with CH3 CH2 OH/H2 O (20/80) at room temperature. After a vacuum concentration, the basic compounds were fixed on an Amberlite IR 120, H sup + form, and eluted with 2 mol/l NH4 OH. The ammoniacal solution was concentrated and lyophilized (2.9 g), and then fractionated twice successively on a chromatography column filled with silica gel. Fractions containing 4-hydroxyisoleucine (determination by thin layer chromatography [TLC] and high-performance liquid chromatography [HPLC]) were pooled). Purification and repeated crystallizations gave 0.6 g pure 4-hydroxyisoleucine (overall yield from dried plant material, 0.56% wt/wt). HPLC analysis of 4-hydroxyisoleucine was carried out on a Shimadzu HPLC (LC. 6A) apparatus equipped with a Shimadzu fluorimeter (RF 530, Kyoto, Japan). We used a highly sensitive method based on precolumn formation of a derivative with O-phtaldialdehyde [13]. Separation was performed on a reverse phase column (Adsorbosphere OPA HS 100 x 4.6 mm, 5 micro m) with an elution gradient composed of CH3 COONa 65 mmol/l, 5% tetrahydrofurane (pH 5.7), and methanol. Detection was carried out by fluorescence analysis (lambda excitation, 355 nm; lambda emission, 410 nm). The chromatograph results revealed one well-separated peak (retention time 8 min, 14 s). All the physicochemical analyses ([alpha]20D, IR spectra, mass spectra, fast atom bombardment [FAB] mode,1 H and13 C nuclear magnetic resonance [NMR] spectra) indicate that the substance isolated from fenugreek seeds in 4-hydroxyisoleucine (molecular formula: C6 H13 O3 N with 2S, 3R, 4S configuration). Pharmacological procedures Rat pancreas isolation. Adult male Wistar rats weighing between 330 and 350 g were used in this study. The surgical procedure was described previously [14]. Rats were anesthetized with sodium pentobarbitone (60 mg/kg i.p.). The pancreas was totally isolated and perfused through its own arterial system with a Krebs-Ringer bicarbonate buffer containing 2 g/l bovine serum albumin and glucose at appropriate concentrations. The solution had the following ionic composition (in millimoles per liter): NaCl 108, KH sub 2 PO4 1.19, KCl 4.74, CaCl2 2.54, MgSO4 [centered dot] 7H sub 2 O 1.19, and NaHCO2 18. An O2/CO2 (95/5) mixture was continuously bubbled through this medium, while maintaining a pH level of 7.4. The preparation was kept at 37.5 degrees C and perfused at a constant pressure, selected to give a flow rate of 2.5 ml/min at the end of the stabilization period. Any change in pancreatic vascular resistance was thus detected by measuring the flow rate. In all experiments, there was a 30-min adaptation period before taking the first sample. Two more samples were taken at 40 and 45 min, with the 45-min time representing the reference value. 4-Hydroxyisoleucine was then perfused for 30 min or 10 min. Indeed, in some experiments, the duration of 4-hydroxyisoleucine perfusion was reduced to 10 min because of the scarceness of the drug. The effluent was collected for 1 min for each sample, which was then immediately frozen for pancreatic hormone (insulin, glucagon, somatostatin) radioimmunoassays. Rat islet isolation. Islets were isolated after collagenase digestion of the pancreas from adult Wistar rats [15]. Immediately after isolation, the islets were preincubated for 90 min at 37.5 degrees C in a Krebs-Ringer bicarbonate buffer (pH 7.4) containing 1 g/l bovine serum albumin and 8.3 or 3 mmol/l glucose. Thereafter, batches of three islets were incubated in the presence of the appropriate glucose concentration (8.3 or 3 mmol/l) for 60 min in 1 ml medium. In these conditions, two experimental sets were performed; first, in the presence of 8.3 mmol/l glucose, the effects of different concentrations of 4-hydroxyisoleucine alone on insulin release were tested; second, a possible interaction of 4-hydroxyisoleucine on the insulin secretion induced by different other secretagogues (L-leucine, L-arginine, tolbutamide, D-glyceraldehyde) was also investigated in the presence of 3 mmol/l glucose, a concentration chosen to avoid interaction of glucose with 4-hydroxyisoleucine and other secretagogues. At the end of each incubation period, an aliquot of the medium was frozen for insulin radioimmunoassay. Human organ donors and procurement of pancreatic tissue. Human pancreases were obtained from brain-dead organ donors in the context of a human islet transplantation protocol, essentially as reported previously [16]. The protocol was approved by the hospital ethics committee, and in all cases informed consent was obtained from family members. After perfusion and extraction, organs were maintained at 4 degrees C for 2-6 h in a solution developed by the University of Wisconsin. Human pancreatic islets were isolated after a modification of Ricordi’s automatic digestion technique. For experiments described in this study, purification of pancreatic islets was accomplished by hand-picking under a stereomicroscope to ensure a comparable degree of purity in the different samples. Positive identification of islets was confirmed by staining aliquots with dithizone [17]. For measuring insulin release, groups of eight islets were incubated for 90 min at 37 degrees C in 1.0 ml bicarbonate-buffered medium, as described elsewhere [17]. After removal of the incubation medium, the same islets were sonicated at 4 degrees C in 0.5 ml acid-alcohol (ethanol 75%, H2 O 23.5%, HCl 10N 1.5%) for the measurement of their insulin content. Assays. Insulin concentrations were measured by the method of Herbert et al. [18] using an antibody supplied by Miles Laboratories (Paris).125 I-labelled insulin was obtained from International CIS (Gif-sur-Yvette, France); the standard used was rat insulin (Novo, Copenhagen, Denmark), whose biological activity was 22.3 micro U/ng. The intra- and interassay coefficients of variation were 9 and 13.5%, respectively. The sensitivity was 0.1 ng/ml. For glucagon and somatostatin determinations, samples were collected in chilled tubes containing 100 micro l of a mixture of EDTA (32 mmol/l) and aprotinin (Antagosan, Hoechst Laboratories, Puteaux, France; 10,000 U/ml kallikrein inhibitor). Glucagon concentrations were measured by the method of Unger et al. [19] using BR124 glucagon antiserum from the Institut de Biochimie Clinique (Centre Medical Universitaire, Geneva, Switzerland); the standard used was Novo porcine glucagon. The intra- and interassay coefficients of variation were 10 and 15%, respectively. The sensitivity was 15 pg/ml. The results are expressed as picograms per milliliter equivalents of porcine glucagon. Plasma somatostatin-like immunoreactivity (SLI) was assayed according to the previously described technique [20] using the 80 degrees C antiserum from Dr. R. Unger (Health Science Center, Dallas, Texas). The intra- and interassay coefficients of variation were 10 and 14%, respectively. The sensitivity was 10 pg/ml. Statistical analysis. Results were submitted to analysis of variance followed by the multiple comparison test of Newman-Keuls or to Student’s t test. Drugs. L-leucine, L-arginine, D-glyceraldehyde, and tolbutamide were purchased from Sigma (St. Louis, MO). Collagenase for pancreatic digestion was also obtained from Sigma. Aprotinin (Antagosan) was kindly supplied by Hoechst Laboratories (Puteaux, France). RESULTS Insulin release from isolated rat islets Effects of 4-hydroxyisoleucine in the presence of glucose. In the presence of 8.3 mmol/l glucose, 4-hydroxyisoleucine (200 micro mol/l) induced a significant increase in insulin release (4.8 +/- 0.3 vs. 3.5 +/- 0.2 ng [centered dot] islet sup -1 [centered dot] h sup -1 in controls, P < 0.01). This effect was concentration dependent in the range of 200-1,000 micro mol/l (Figure 1). These concentrations were much lower than those required for the stimulating effect of structural amino acid analogs such as leucine or isoleucine. A significant (P < 0.05) effect was obtained with L-leucine and L-isoleucine at concentrations of 5 and 3 mmol/l, respectively (6.3 +/- 1.0 and 5.6 +/- 0.7 vs. 3.4 +/- 0.3 ng [centered dot] islet sup -1 [centered dot] h sup -1 in controls). Homoserine was completely ineffective in the range of 200 micro mol/l to 20 mmol/l (4.1 +/- 0.4 to 4.3 +/- 0.5 vs. 3.7 +/- 0.5 ng [centered dot] islet sup -1 [centered dot] h sup -1 in controls). [Help with image viewing] ——————————————————————————– Figure 1. Effect of 4-hydroxyisoleucine on insulin release from isolated rat islets in the presence of 8.3 mmol/l. Values are means +/- SE from at least 10 different experiments. **P < 0.01, ***P < 0.001. ——————————————————————————– Effect of 4-hydroxyisoleucine in the presence of other secretagogues. In the presence of 3 mmol/l glucose, 4-hydroxyisoleucine at the concentration of 200 micro mol/l was ineffective on insulin release (1.9 +/- 0.2 vs. 1.7 +/- 0.1 ng [centered dot] islet sup -1 [centered dot] h sup -1). In the same experimental conditions, tolbutamide (200 micro mol/l), L-arginine (20 mmol/l), L-leucine (10 mmol/l), and D-glyceraldehyde (5 mmol/l) elicited a significant (P < 0.05) increase in insulin release (Figure 2). 4-Hydroxyisoleucine (200 micro mol/l) did not modify the insulin-stimulating effect of these secretagogues. [Help with image viewing] ——————————————————————————– Figure 2. Effect of 4-hydroxyisoleucine (200 micro mol/l) on insulin release induced by other secretagogues in isolated rat islets incubated in the presence of 3 mmol/l glucose. Effects of each secretagogue alone ([white square with dot fill]): tolbutamide (200 micro mol/l), L-arginine (20 mmol/l), L-leucine (10 mmol/l), and D-glyceraldehyde (5 mmol/l). Effects of each secretagogue plus 4-hydroxyisoleucine ([square with orthogonal crosshatch fill]). Values are means +/- SE from at least seven different experiments. Control experiments © with glucose alone; *P < 0.05; **P < 0.01. ——————————————————————————– Pancreatic hormones secretion from isolated perfused rat pancreas. In isolated pancreas, perfused in the presence of a slightly stimulating glucose concentration (8.3 mmol/l), 4-hydroxyisoleucine at a concentration of 200 micro mol/l elicited an immediate insulin response, which persisted during the 30 min of administration (Figure 3). The pattern of this response was clearly biphasic: the first phase peaked at +187 +/- 39% (2 min, P < 0.01) of basal values and was followed by a second phase throughout the amino acid perfusion. At the end of the drug administration, insulin output progressively returned to basal values. In the same experimental conditions, the drug did not modify either the pancreatic flow rate or the glucagon and somatostatin pancreatic secretions (Table 1). [Help with image viewing] ——————————————————————————– Figure 3. Effect of 4-hydroxyisoleucine on insulin secretion in isolated perfused rat pancreas in the presence of 8.3 mmol/l glucose. 4-Hydroxyisoleucine was perfused at 200 micro mol/l during 30 min ([black circle]), and [white circle] represents control experiments. The results are expressed as changes in percentage of the value at time 45 min, taken as reference (100%). Values are means +/- SE of seven to nine experiments. The insulin output rate (ng/min) at 45 min was 12.6 +/- 1.8 and 15.0 +/- 2.1 for each set of experiments, respectively. ——————————————————————————– [Help with image viewing] ——————————————————————————– Table 1. Effects of 4-hydroxyisoleucine on insulin, glucagon, and somatostatin secretions and pancreatic flow rate in isolated perfused normal rat pancreas ——————————————————————————– Interestingly, the stimulating effect of 4-hydroxyisoleucine was clearly related to the glucose concentration in the perfusion medium (Figure 4A). Indeed, 4-hydroxyisoleucine (200 micro mol/l) was ineffective in the presence of 5 mmol/l glucose (Figure 4B). In the presence of 6.6 mmol/l glucose, the amino acid elicited a weak and transient insulin response (+3.7 +/- 1.2 ng/min at 2 min); the stimulating effect of 4-hydroxyisoleucine was more pronounced in the presence of 8.3 mmol/l glucose (+18.3 +/- 5.8 ng/min at 2 min). Finally, the drug induced a biphasic and long-lasting stimulation of insulin secretion in the presence of 10 mmol/l glucose (+47.6 +/- 5.2 ng/min at 2 min). [Help with image viewing] ——————————————————————————– Figure 4. The insulin-stimulating effect of 4-hydroxyisoleucine (200 micro mol/l) is related to the concentration of glucose in the medium. A: Relationship between the maximal increment of insulin secretion and the glucose concentration in the medium. These increments express the difference between secretion at 47 min and basal secretion at 45 min. B: Kinetics of insulin secretion in the presence of 5 mmol/l ([white square]), 6.6 mmol/l ([white up-pointing triangle]), 8.3 mmol/l ([black up-pointing triangle]), and 10 mmol/l ([black circle]) glucose. Values are means +/- SE of five to nine experiments. ——————————————————————————– Insulin release from human pancreatic islets. Measurements of insulin release and content in the presence of 8.3 mmol/l of glucose and 4-hydroxyisoleucine at different concentrations (100-1,000 micro mol/l) revealed that this amino acid stimulates insulin release without affecting insulin content. The amino acid induced a significant increase (P < 0.05) from a concentration of 100 micro mol/l (Table 2). [Help with image viewing] ——————————————————————————– Table 2. Effects of 4-hydroxyisoleucine on insulin release and insulin content of human pancreatic islets ——————————————————————————– Moreover, the stimulatory effect of 4-hydroxyisoleucine at the concentration of 200 micro mol/l was studied in the presence of different glucose concentrations (3, 8.3, and 16.7 mmol/l). Ineffective in the presence of 3 mmol/l glucose, 4-hydroxyisoleucine significantly potentiated the insulin release induced by 8.3 mmol/l (P < 0.05) or 16.7 mmol/l (P < 0.05) glucose (Figure 5). [Help with image viewing] ——————————————————————————– Figure 5. The stimulating effect of 4-hydroxyisoleucine on insulin release from human islets is related to the concentration of glucose in the medium ([white square]) control experiments ([black square]). Values (mean +/- SE of 17-22 determinations) are expressed as picomoles per eight islets per 90 min. *P < 0.05 vs. control islets. ——————————————————————————– DISCUSSION The results of the present study demonstrate that 4-hydroxyisoleucine, an amino acid extracted and purified from fenugreek seeds, is a novel potentiator of insulin secretion. It is worthy to mention that this amino acid is not present in mammalian tissues but only found in plants, especially in Trigonella species. Isolated and purified according to the procedures we developed, it is mainly distributed in fenugreek seeds in which it accounts for 80% of the total content in free amino acids [21]. Consequently, it may be considered as a novel pharmacological substance. In a previous report, Madar et al. [10] have shown that the daily administration of ground fenugreek seeds are able to lower blood glucose levels in NIDDM subjects. Since fenugreek seeds contain a high percentage of dietary fiber (60%), these authors proposed this latter fraction to be the major contributor for reducing the plasma glucose level. However, owing to 1) the high content of 4-hydroxyisoleucine in the seeds (0.5% wt/wt) and to 2) the low threshold concentration for this amino acid to stimulate insulin release in human islets, we can suggest that 4-hydroxyisoleucine might, at least in part, account for fenugreek antidiabetic effects in NIDDM. The present data show that 4-hydroxyisoleucine stimulates insulin secretion through a direct action on pancreatic beta-cells. Indeed, the amino acid is effective both in the isolated perfused pancreas and isolated islets from rats. The target of 4-hydroxyisoleucine in endocrine pancreas seems to be exclusively beta-cells, since no change in pancreatic glucagon, somatostatin secretions, or in pancreatic vascular resistance was observed. Thus the activity of this amino acid contrasts with the effects of other insulin secretory amino acids such as arginine [22,23]. Moreover, our results show that 4-hydroxyisoleucine is effective on insulin release in a much lower concentration range than its structural amino acids congeners. In our experimental conditions, the drug is 25 and 15 times more effective than leucine or isoleucine, respectively. The originality of this amino acid is strengthened by our studies concerning the effects of the drug on the insulin response to other secretagogues. Indeed, we investigated the effects of four insulinotropic substances well known to stimulate insulin release, in basal conditions, by different mechanisms (beta-cell membrane depolarization related or not to metabolic events). Neither the stimulatory effects of tolbutamide and L-arginine nor those of L-leucine and D-glyceraldehyde were modified by the addition of 4-hydroxyisoleucine (200 micro mol/l). Thus it appears that, unlike as for glucose, this drug does not interact with these secretagogues. It must be emphasized that 4-hydroxyisoleucine is devoid of any secretory effect under normal concentrations of glucose (5 mmol/l) mimicking normoglycemia. In contrast, the insulinotropic activity appeared and strongly developed upon increasing glucose concentrations to supranormal levels. To counteract the deficiency of insulin secretion present in NIDDM [24-26], sulfonylureas are currently the only therapeutic tool available. However, a common drawback of sulfonylureas is the risk of severe hypoglycemia [27,28]. It seems worthwhile to search for other insulin-stimulatory agents, which may provide an alternative strategy for the treatment of the disease. From this point of view, it has to be emphasized that the glucose dependency of the response to 4-hydroxyisoleucine may be of interest in vivo in avoiding the risk of hypoglycemia. In summary, because of 1) the insulinotropic activity of this amino acid, only in the presence of supranormal levels of glucose, 2) the great sensitivity of human beta-cells to this amino acid, and 3) the absence of acute toxicity (1 g/kg i.p. in mice, J.J. Serrano, personal communication), we conclude that 4-hydroxyisoleucine may be considered as a novel pharmacological insulinotropic compound potentially useful for the development of an alternative strategy in the treatment of NIDDM. The results of this study have led to a patent (Y.S., G.R., inventors; Jouvenet, assignee. Composition capable of stimulating insulin secretion intended for the treatment of non insulin-dependent diabetes. Fr Demande FR 2,695,317; 10 Mar 1995. U.S. patent 5,470,879; 28 Nov 1995. Eur. pat. appl. EP0,587,476). ACKNOWLEDGMENTS This study was supported by a grant from Societe Civile Jouvenet, Paris, France. We thank M. Jacob (URA CNRS 0468, Universite Montepellier II, France) for reading the manuscript, M.A. Garcia and V. Montesinos for manuscript preparation, and M. Tournier for technical assistance. REFERENCES 1. Cerasi E, Luft R: The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus. Acta Endocrinol 55:278-304, 1967 [Medline Link] [Context Link] 2. De Fronzo RA: The triumvirate: beta-cell, muscle, liver: a collusion responsible for NIDDM. Diabetes 37:667-687, 1988 [Medline Link] [BIOSIS Previews Link] [Context Link] 3. Kahn SE, Porte D: Islet dysfunction in non-insulin-dependent diabetes mellitus. Am J Med 85:4-8, 1988 [Medline Link] [BIOSIS Previews Link] [Context Link] 4. Girard J: Role of insulin resistance in type 2 diabetes. Diabetes Metab, 20:330-336, 1994 [Medline Link] [BIOSIS Previews Link] [Context Link] 5. 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      Pennherbco.com has fennugreek seeds for $5.50 per pound or $5.25 for 60 800mg capsules.

      But does anyone know the effective does for using it post workout? I didn’t pick it up while skimming the above.




      I must say i truly admire your ability to find effectiveness in even the most obscure of item….but damn are you cheap ! haha…I bet you’d steal Christ from the cross and then go back for the nails… …However in one of the abstracts above, it mentioned that only a specific isomer was shown to be effective. I’m quite curious about this product ..I saw that it is an ingredient in VPX’s new creatine formula..”Plasma Xpandor”(I understand that their pro hormones are not the greatest…but some stuff seems interesting otherwise)..I also wonder if Syntrax will include it as part of their new upgrade of FUZU?



      in reality im not actually cheap, i never go to sales im a stickler for name brands (with clothes and such) but with stuff like this when you could easily put together a stack in 30 items to bulk with and if you don’t watch it pay 25$ for each other them… it becomes very ineffective.

      Most people are going to buy creatine and whey at least that could easily cost them $100 or so at GNC for a months supply that along with ~35$ for the gym fee… and what are going to gian in that month 3 pounds maybe?

      I love supplements, hence the name, and if I can find a way to feasibly take every effective thing I know of then why not.



      Supnut…. I’m with you. Actually I love being on the gear but when I’m not I love using supplements. A lot of guys wonder how I can maintain my size and strength while not on the gear and the answer is proper supplementation. Cheers.

      BTW…… I have a feeling that this is one of those supplements that you won’t really feel or get much from. Probably there are better things to spend your money on. Cheers.

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