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PubMed2005

[Study on D-glucosamine-zn (II) complexes by IR spectral analysis].

In this paper, a series of glucosamine-Zn(II) complexes were synthesized by the reaction of D-glucosamine hydrochloride with ZnSO4 at different pH values. The physical properties and the IR spectra of glucosamine-ZnSO4 complexes were investigated. The absorption at 3346 and 3292 cm(-1) shifted to 3300 cm(-1) due to O--H and N--H stretching, one at 1617 cm(-1) shifted to 1530 cm(-1) due to N-H stretching, and one at 1094 cm(-1) disappeared due to secondary alcohol --OH stretching. But 1033 cm(-1) with primary alcohol --OH did not shift, suggesting that both the amino and secondary hydroxyl groups of glucosamine are coordinated to Zn(II). The results showed that the coordination ability of Zn(II) to glucosamine was enhanced with the pH value increasing, however, the coordination ability weakened when pH value was more than 6.5. So pH 6.5 is an optimal coordination condition for glucosamine-ZnSO4 complexes. The complexes of D-glucosamine with different zinc salts (zinc sulfate, zinc nitrate, zinc acetate, and zinc chloride) were also synthesized at the same pH value, and zinc chloride had weaker coordination ability than other zinc salts. Their IR spectra indicated that glucosamine-Zn(II) complexes with different zinc salts had different coordination model, and only glucosamine-ZnSO4 complex had fixed ratio of coordination under the condition of pH 6.5. The structure of the complex seems to correspond to [Zn(glucosamine)]SO4 7H2O at pH 6.5.

Chlorides↗

PubMed2006

High performance liquid chromatography for the determination of glucosamine sulfate in human plasma after derivatization with 9-fluorenylmethyl chloroformate.

In this study, we developed a simple, rapid, sensitive, and reliable method for the determination of glucosamine sulfate in human plasma, which was based on derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) followed by reverse-phase HPLC-FLD. For the first time, FMOC-Cl was introduced into derivatization of glucosamine sulfate in human plasma. The amino groups of glucosamine sulfate and vertilmicin sulfate (the internal standard) were trapped with FMOC-Cl to form glucosamine-FMOC-Cl and vertilmicin-FMOC-Cl adducts, which can be very suitable for HPLC-FLD. Precipitation of plasma proteins by acetonitrile was followed by vortex mixing and centrifugation. Chromatographic separation was performed on a C18 column (DIAMONSIL 150 x 4 mm id, 5 microm) with a mobile phase gradient consisting of acetonitrile and water at a flow-rate of 1 mL/min. The retention times of glucosamine-FMOC-Cl and vertilmicin-FMOC-Cl adducts were 8.9 and 21.2 min, respectively. This method was shown to be selective and sensitive for glucosamine sulfate. The limit of detection was 15 ng/mL for glucosamine sulfate in plasma and the linear range was 0.1-10 mg/mL in plasma with a correlation coefficient (r) of 0.9999. The relative standard deviations (RSDs) of intra-day and inter-day assays were 5.2-8.1% and 6.1- 8.5%, respectively. Extraction recoveries of glucosamine sulfate in plasma were greater than 90%. The validated method was successfully applied to the determination of glucosamine sulfate in human plasma samples.

Blood Chemical Analysis↗

PubMed2000

Development and comparison of two 3T3-L1 adipocyte models of insulin resistance: increased glucose flux vs glucosamine treatment.

Insulin resistance can be induced in vivo by intravenous infusion of glucosamine or in cells by incubation with glucosamine. However, a publication (Hresko, R. C., et al. (1998) J. Biol. Chem. 273, 20658-20668) suggests a trivial explanation of glucosamine-induced insulin resistance whereby intracellular ATP pools are depleted presumably due to the phosphorylation of glucosamine to glucosamine 6-phosphate, a hexosamine pathway intermediate. The reduced ATP level impaired insulin receptor (IR) autophosphorylation and tyrosine kinase activity toward substrates. The present work describes the development and comparison of two methods for inducing insulin resistance, by treating 3T3-L1 adipocytes overnight using either 25 mM glucose/5 nM insulin or 2 mM glucosamine. Under these conditions basal glucose transport rates were comparable with controls. Insulin-stimulated 2-deoxyglucose uptake, however, was reduced by approximately 45% in response to both high glucose/insulin and glucosamine treatment, relative to control cells. The total relative amounts of the insulin-responsive glucose transporter, Glut4, remained constant under both treatment conditions. The relative phosphotyrosine (Tyr(P)) contents of the insulin receptor and its substrate 1 (IRS-1) were assessed in whole cell homogenates. With both methods to induce insulin resistance, IR/IRS-1 Tyr(P) levels were virtually indistinguishable from those in control cells. Insulin-stimulated phosphorylation of Akt on Ser(473) was not impaired in insulin-resistant cells. Furthermore, the relative Tyr(P) content of the PDGF receptor was comparable in high glucose/insulin- or glucosamine-treated 3T3-L1 adipocytes upon subsequent challenge with PDGF. Finally, the relative amounts of glutamine:fructose-6-phosphate amidotransferase and O-linked N-acetylglucosamine transferase, two important hexosamine pathway enzymes, were similar in both treatments when compared with controls. Thus, 3T3-L1 adipocytes can be used as a model system for studying insulin resistance induced by increased influx of glucose. Under appropriate experimental conditions, glucosamine treatment can mimic the effects of increased glucose flux without impairment of tyrosine phosphorylation-based signaling.

3T3 Cells↗

PubMed2002

Glucose transport by osmotic shock and vanadate is impaired by glucosamine.

In 3T3-L1 adipocytes, we previously reported that glucosamine impairs insulin stimulation of glucose transport, which is accompanied by impaired insulin stimulation of serine/threonine kinase Akt. To examine the role of Akt in glucosamine-induced insulin resistance, we investigated time course for insulin stimulation of Akt activity and glucose transport during recovery from glucosamine-induced insulin resistance. After induction of insulin resistance by glucosamine, we washed cells to remove glucosamine and incubated them for various times. After one hour, insulin stimulated-glucose transport was significantly increased and continued to increase up to 6-24 h. Insulin stimulation of Akt, however, did not increase after 1-3 h and began to slightly increase after 6 h. Next, we investigated effects of osmotic shock and vanadate on glucose transport in glucosamine-treated cells and found that glucosamine completely inhibited their actions in these cells. These data suggest that an Akt-independent mechanism is operative in glucosamine-induced insulin resistance and glucosamine impairs glucose transport stimulated by various stimuli involving and not involving Akt activation.

Adipocytes↗

PubMed2005

Glucosamine-induced phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 is mediated by the protein kinase R-like endoplasmic-reticulum associated kinase.

In diabetic animals, enhanced production of vascular endothelial growth factor is thought to be a major contributor to the development of diabetic retinopathy. In the present study, glucosamine-treated R28 retinal neuronal cells were used as an experimental model system to explore the possible involvement of the hexosamine biosynthetic pathway in the diabetes-induced changes in mRNA translation. Glucosamine treatment enhanced vascular endothelial growth factor production subsequent to changes in phosphorylation of the alpha-subunit of eukaryotic initiation factor 2, with no change in vascular endothelial growth factor mRNA content. Possible mechanisms through which glucosamine might act to increase eukaryotic initiation factor 2alpha phosphorylation include enhanced O-linked glycosylation of protein kinase or phosphatase regulatory proteins and/or induction of oxidative stress. However, increasing global protein O-glycosylation through inhibition of O-beta-N-acetylglucosaminidase did not mimic the effect of glucosamine on eukaryotic initiation factor 2alpha phosphorylation. Likewise, attenuating glucosamine-induced oxidative stress with two different antioxidants did not reduce glucosamine-induced eukaryotic initiation factor 2alpha phosphorylation. Glucosamine treatment was also found to promote eukaryotic initiation factor 2alpha phosphorylation in wild-type mouse embryonic fibroblasts, but not in mouse embryonic fibroblasts lacking the eukaryotic initiation factor 2alpha kinase referred to as RNA-dependent protein kinase-like endoplasmic-reticulum associated kinase, implicating the kinase in the glucosamine-induced increase in eukaryotic initiation factor 2alpha phosphorylation. Overall, the results are consistent with glucosamine causing activation of RNA-dependent protein kinase-like endoplasmic-reticulum associated kinase, which phosphorylates eukaryotic initiation factor 2alpha and consequently upregulates translation of mRNAs encoding specific proteins, such as vascular endothelial growth factor.

Animals↗

PubMed2005

The antioxidant activity of glucosamine hydrochloride in vitro.

The antioxidant potency of chitin derivative-glucosamine hydrochloride was investigated employing various established in vitro systems, such as superoxide (O2*-)/hydroxyl (*OH)-radical scavenging, reducing power, and ferrous ion chelating potency. As expected, we obtained several satisfying results, as follows: first, glucosamine hydrochloride had pronounced scavenging effect on superoxide radical. For example, the O2*- scavenging activity of glucosamine hydrochloride was 83.74% at 0.8 mg/mL. Second, the *OH scavenging activity of glucosamine hydrochloride was also strong and was about 54.89% at 3.2 mg/mL. Third, the reducing power of glucosamine hydrochloride was more pronounced. The reducing power of glucosamine hydrochloride was 0.632 at 0.75 mg/mL. However, ferrous ion-chelating potency was soft. Furthermore, ferrous ion-chelating potency, the scavenging rate of radical, and the reducing power of glucosamine hydrochloride increased with their increasing concentration, and they were concentration dependent. The multiple antioxidant activity of glucosamine hydrochloride was evident as it showed considerable reducing power, superoxide/hydroxyl-radical scavenging ability. These in vitro results suggest the possibility that glucosamine hydrochloride could be effectively employed as an ingredient in health or functional food, to alleviate oxidative stress.

Antioxidants↗

PubMed1985

Reactivity of Glu-22(beta) of hemoglobin S for amidation with glucosamine.

X-ray diffraction analysis of deoxyhemoglobin S crystals has implicated that a number of carboxyl groups of the protein are present at or near the intermolecular contact regions. The reactivity of these or other carboxyl groups of hemoglobin S for the amidation with an amino sugar, i.e., glucosamine, and the influence of amidation on the oxygen affinity and polymerization have been investigated. Reaction of oxyhemoglobin S at pH 6.0 and 23 degrees C with 20 mM 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 100 mM [3H]glucosamine for 1 h resulted in an incorporation of nearly two residues of glucosamine per tetramer. The amidation was very specific for the carboxyl groups of globin; the glucosamine was not incorporated into the heme carboxyls. Derivatization of hemoglobin S by glucosamine increased the O2 affinity of the protein but had no influence on either the Hill coefficient or the Bohr effect. Amidation by glucosamine also increased the solubility of deoxyhemoglobin S by about 55%. Tryptic peptide mapping of the modified hemoglobin S indicated that the peptides beta-T3 and beta-T5 contained the glucosamine incorporated into the protein. Sequence analysis of glucosamine-modified beta-T3 and beta-T5 demonstrated that the gamma-carboxyl groups of Glu-22 and Glu-43, respectively, had been derivatized with glucosamine. The residue Glu-43(beta) shows a high selectivity toward glycine ethyl ester also, whereas Glu-22(beta) is not reactive toward this amine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed2002

High doses of glucosamine-HCl have detrimental effects on bovine articular cartilage explants cultured in vitro.

OBJECTIVE: To investigate both the biochemical and the potential morphological changes in bovine cartilage explants following treatment with glucosamine HCl, and to evaluate the capability of glucosamine to counteract the degradation of cartilage induced by catabolic agents such as interleukin-1beta (IL-1beta) and the bacterial lipopolysaccharide (LPS). DESIGN: Bovine articular cartilage explants were treated with increasing doses of glucosamine HCl (0.25-25mg/ml) in the absence or in the presence of IL-1beta or LPS. The release of matrix proteoglycans in the medium, as well as variations in nitric oxide and lactate production were evaluated by standard assays. Proteoglycan synthesis was determined by incorporation of Na(2)-(35)SO(4). Ultrastructural analysis was performed by transmission electron microscopy. RESULTS: Increasing doses of glucosamine (2.5, 6.5, 25mg/ml) induced a dose-dependent decrease in proteoglycan synthesis and in lactate production after 24h treatment. The biochemical changes induced by IL1-beta or LPS appeared to be inhibited by 6.5 and 25mg/ml glucosamine. At these concentrations a decrease in cell viability was observed, which reached over 90% at 25mg/ml. CONCLUSIONS: This study shows that pharmacological doses of glucosamine induce a broad impairment in the metabolic activity of bovine chondrocytes, leading to cell death. The inhibition of the catabolic effects induced by IL1-beta and LPS appears related to glucosamine toxicity. In other experimental models, the same or similar doses of glucosamine have previously been used, without showing any adverse effect. We conclude that, in studying the effects of glucosamine, particular attention should be addressed to the experimental model, the doses and the length of treatment. Published by Elsevier Science Ltd. All rights reserved.

Animals↗

PubMed1980

Membrane-active drugs potentiate the killing of tumor cells by D-glucosamine.

D-Glucosamine is toxic to several malignant cell lines and in vivo tumors at concentrations that have little effect upon normal host tissues. Evidence is presented to support the hypothesis that cellular membranes may be the primary targets of glucosamine's tumoricidal activity. Treatment of rat C6 glioma cells with a cytotoxic concentration of glucosamine (20 mM) caused fragmentation of rough endoplasmic reticulum, proliferation of Golgi complexes, evagination of outer nuclear and mitochondrial membranes, and the accumulation of membranous vacuoles and lipid droplets in the cytoplasm. These changes were detected within the first 3 hr after treatment of cultures with glucosamine and became increasingly severe until cell lysis occurred between 24 and 48 hr of treatment. The cytotoxicity of glucosamine was potentiated by the local anesthetic lidocaine, and by other membrane-active drugs, at concentrations that were growth inhibitory but nonlytic. Most of these drugs possessed local anesthetic activity and inhibited glioma sterol synthesis. Within the same period of time required for ultrastructural changes in cellular membranes, glucosamine inhibited the incorporation of [2-(14)C]acetate into sterols and into an unidentified 400-dalton lipid that migrated close to sterols on thin-layer chromatograms. This inhibition was potentiated by lidocaine and increased over the same range of D-glucosamine concentrations that led to increased cell toxicity after a 48-hr treatment. These findings suggest that the effects of glucosamine upon cellular membranes may be central to its tumoricidal activity and that glucosamine, in combination with membrane-active drugs, may be useful in the treatment of certain types of tumors, particularly those of the central nervous system.

Anesthetics, Local↗

PubMed2002

Glucosamine-induced beta-cell dysfunction: a possible involvement of glucokinase or glucose-transporter type 2.

INTRODUCTION: The mechanism for beta-cell dysfunction induced by glucosamine has not yet fully been investigated previously. AIM: To investigate the effects of glucosamine on insulin release or gene expression related to glucose metabolism in rat islets cultured with glucosamine for 24 hours. METHODOLOGY: After islets were cultured with glucosamine or diazoxide, we measured glucose- or arginine-induced insulin release by using radioimmunoassay (RIA) and gene expressions by semiquantitative polymerase/chain reaction. RESULTS: Coculture with glucosamine inhibited 27 mmol/L glucose-induced insulin release with no effects on 20 mmol/L arginine-induced insulin release. Coculture with diazoxide did not restore the impaired glucose-induced insulin release. In glucosamine-cultured islets, glucose-transporter type 2 or glucokinase mRNA expression decreased, whereas hexokinase mRNA increased. Phosphofructokinase-A, pyruvate dehydrogenase E1alpha, or pyruvate carboxylase mRNA was not affected by the addition of glucosamine. Pancreatic and duodenal homeobox-1, preproinsulin, or p21 (induced by oxidative stress) mRNA expression did not change, whereas uncoupling protein 2 mRNA, which plays an important role in thermogenesis, decreased in glucosamine-cultured islets. CONCLUSION: These data imply that glucosamine impairs glucose-induced insulin release probably through the inhibition of glucose metabolism.

Animals↗

PubMed2000

Glucosamine-induced insulin resistance in 3T3-L1 adipocytes.

To study molecular mechanisms for glucosamine-induced insulin resistance, we induced complete and reversible insulin resistance in 3T3-L1 adipocytes with glucosamine in a dose- and time-dependent manner (maximal effects at 50 mM glucosamine after 6 h). In these cells, glucosamine impaired insulin-stimulated GLUT-4 translocation. Glucosamine (6 h) did not affect insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 and -2 and weakly, if at all, impaired insulin stimulation of phosphatidylinositol 3-kinase. Glucosamine, however, severely impaired insulin stimulation of Akt. Inhibition of insulin-stimulated glucose transport was correlated with that of Akt activity. In these cells, glucosamine also inhibited insulin stimulation of p70 S6 kinase. Glucosamine did not alter basal glucose transport and insulin stimulation of GLUT-1 translocation and mitogen-activated protein kinase. In summary, glucosamine induced complete and reversible insulin resistance in 3T3-L1 adipocytes. This insulin resistance was accompanied by impaired insulin stimulation of GLUT-4 translocation and Akt activity, without significant impairment of upstream molecules in insulin-signaling pathway.

3T3 Cells↗

PubMed1995

Possible involvement of dihydrofructosazine in the DNA breaking activity of D-glucosamine.

Dehydrochlorination of D-glucosamine (2-amino-2-deoxy-D-glucose) hydrochloride with an anion exchange resin made its DNA breaking activity in plasmid pBR322 much higher, especially in the presence of Cu2+. The sample of anion exchanger-treated D-glucosamine hydrochloride, i.e., HCL-free D-glucosamine sample, showed an absorption maximum at 274 nm on the UV absorption spectrum in water as seen in the case of fructosazine [2,5-bis(D-arabino-tetrahydroxybutyl)pyrazine] one of the dimers of D-glucosamine. On a positive-ion fast atom bombardment (FAB) mass spectrum, the sample showed an ion peak at m/z 323 as a base peak, corresponding to dihydrofructosazine [2,5-bis(D-arabino-tetrahydroxybutyl) dihydropyrazine], which was a precursor of fructosazine, as well as those of D-glucosamine itself (m/z 180) and fructosazine (m/z 321). The DNA strand breaking activity of HCL-free D-glucosamine sample was directly proportional to the peak intensity of m/z 323 ion, while the DNA breaking activity of fructosazine was much weaker than that of HCL-free D-glucosamine sample. 2,5-Dihydro-3,6-dimethylprazine and 2,3-dihydro-5,6-dimethylpyrazine having a dihydropyrazine skeleton the same as dihydrofructosazine showed the same extent of DNA strand breaking activity as did the HCL-free D-glucosamine sample. These results indicated that dihydrofructosazine produced during the dehydrochlorination is closely involved in the DNA breaking activity of HCL-free D-glucosamine sample.

DNA Damage↗

PubMed1980

Effect of D-glucosamine on growth and several functions of cultured mastocytoma P-815 cells.

In order to elucidate the biochemical basis for the selective cytotoxicity of D-glucosamine to neoplastic cells, the effect of glucosamine on the growth and several functions of mastocytoma P-815 cells were examined. Incubation of mastocytoma cells with 5 mM glucosamine resulted in a marked inhibition of growth and a significant reduction of cellular uptake and oxidation of glucose and of cellular levels of adenosine triphosphatase (ATP). Glucosamine also reduced the uridine nucleotide pool sizes, and accumulated uridine diphosphate (UDP)-N-acetylglucosamine. However, growth inhibition by glucosamine, which was reversed by glucose, was not prevented by exogenous uridine. In addition, glucosamine suppressed the phosphorylation of thymidine and its incorporation into deoxyribonucleic acid (DNA). The suppression of cell division by glucosamine was accompanied by the elevation of several functions of mastocytoma cells, including the accumulation of adenosine-3', 5'-monophosphate (cAMP), histamine, and serotonin. The incorporation of [(35)S]SO(4)(2-) into acidic glycosaminoglycan was also increased. Of these functional alterations, the elevation of cAMP levels was the earliest detectable change, indicating that growth and functions of mastocytoma cells are also regulated by cAMP. However, glucosamine did not affect the adenylate cyclase activity of plasma membrane in vitro, suggesting the necessity of intact membrane structure for the action of glucosamine.

Adenosine Triphosphate↗

PubMed1994

Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats.

A characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) is the lack of an acute insulin response to intravenous glucose with maintenance of the response to other secretagogues. It has been hypothesized that impaired glucose sensing stems from defective beta-cell glucokinase. It remains unclear whether decreased pancreatic glucokinase activity will produce defects of insulin secretion similar to those observed in NIDDM. In this study, the effects of glucosamine on glucokinase activity and on islet function were assessed in vitro and in vivo. Glucosamine (5 mmol/l) reduced glucokinase activity in islet homogenate and diminished the insulin response to glucose (200 mg/dl) by isolated islets, whereas the response to arginine (20 mmol/l at 100 mg/dl glucose) was unaffected. In conscious normal rats, glucosamine lowered plasma insulin, followed by an increase in blood glucose. Administration of glucosamine 10 min before an infusion of glucose (10 mg.min-1. 15 min) reduced the insulin response. The primary effect was an attenuation of the first-phase insulin response relative to the decreased basal insulin levels. Arginine (10 mg.min-1.15 min) induced biphasic insulin release in both groups. Although glucosamine slightly reduced the absolute insulin response, it was normal relative to preinfusion levels. In all experiments, glucagon secretion was unaffected by glucosamine. The results indicate that glucosamine inhibits beta-cell glucokinase activity in vitro. In addition, glucosamine impairs glucose- but not arginine-induced insulin secretion. We conclude that glucosamine, probably via a reduction of glucokinase activity, impairs insulin secretion in a manner comparable to that seen in NIDDM.

Animals↗

PubMed2005

Glucosamine abrogates the acute phase of experimental autoimmune encephalomyelitis by induction of Th2 response.

Glucosamine, a natural glucose derivative and an essential component of glycoproteins and proteoglycans, has been safely used to relieve osteoarthritis in humans. Recent studies have shown that glucosamine also possesses immunosuppressive properties and is effective in prolonging graft survival in mice. Whether this reagent is effective in human multiple sclerosis (MS), an inflammatory demyelination in the CNS, is not known. We thus investigated the therapeutic effect of glucosamine on experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We demonstrated that oral, i.p., or i.v. administration of glucosamine significantly suppressed acute EAE, with reduced CNS inflammation and demyelination. A significant, albeit not strong, blockade of Th1 response and an up-regulation of Th2 cytokines (IL-5 and IL-10) are observed in the splenocytes of glucosamine-treated mice. Glucosamine also regulates IL-5 and IL-10 in vitro. As glucosamine is able to effectively suppress acute EAE, has low or absent toxicity, and has been safely used in humans orally, our study suggests a potential use for this drug alone or in combination with other disease-modifying immunotherapies to enhance their efficacy and reduce their doses in MS and possibly other autoimmune disorders. Furthermore, because glucosamine functions not simply as an immunosuppressant, but as a mild immunomodulator, administration of glucosamine provides a novel immunoregulatory approach for autoimmune disorders.

Administration, Oral↗

PubMed1975

Antigen-enhanced glucosamine incorporation by peritoneal macrophages in cell-mediated hypersensitivity. I. Studies on biology and mechanism.

The interaction between sensitized lymphocytes and specific antigen occurring in classic delayed hypersensitivity causes guinea pig peritoneal macrophages to incorporate increased amounts of glucosamine into TCA precipitable, membrane-associated, cell surface material. Antigen-induced stimulation of glucosamine also occurred in peritoneal exudate cells (PEC) isolated from animals primed for cutaneous basophil hypersensitivity with certain strong antigens (KLH, vaccinia virus) in incomplete Freund's adjuvant (IFA), and lymphocytes from such animals elaborated MIF when cultured with specific antigen. Thus, the use of complete Freund's adjuvant is not obligatory for the induction of sensitized lymphocytes capable of secreting MIF or stimulating macrophage glucosamine incorporation; however, the potency of the immunogen employed is a critical variable since lymphocytes from animals primed with weaker antigens (HSA, BGG) in IFA did not have these capabilities. Significantly enhanced incorporation of radioactive glucosamine by macrophages occurred when normal PEC were cultured in lymphokine-containing supernatants, but the magnitude of incorporation was smaller than that of sensitized PEC stimulated by antigen. The final 24 hr of macrophage culture was critically important because lymphokines were equally effective in promoting glucosamine incorporation when present for only this interval. The kinetics of this response are thus very similar to those reported for macrophage "activation". The mechanism by which sensitized lymphocytes and their products stimulate glucosamine incorporation is not established, but at least part of the increment may be attributed to enhanced transport of glucosamine across the macrophage plasma membrane. The plant lectins Con A and PHA stimulated unsensitized plastic-adherent cells to increased glucosamine in corporation and exerted a further additive stimulation on sensitized PEC when nonadherent sensitized lymphocytes were present. It is likely that these mitogens stimulate glucosamine incorporation by two distinct mechanisms, one involving sensitized nonadherent lymphocytes and a second involving only adherent cells (macrophages and/or plastic adherent lymphocytes.

Animals↗

PubMed2002

Inhibitory actions of glucosamine, a therapeutic agent for osteoarthritis, on the functions of neutrophils.

Glucosamine, an amino monosaccharide naturally occurring in the connective and cartilage tissues, contributes to maintaining the strength, flexibility, and elasticity of these tissues. In recent years, glucosamine has been used widely to treat osteoarthritis in humans and animal models. Neutrophils, which usually function as the primary defenders in bacterial infections, are also implicated in the destructive, inflammatory responses in arthritis. In this study, we have evaluated the effects of glucosamine on neutrophil functions using human peripheral blood neutrophils. Glucosamine (0.01-1 mM) dose-dependently suppressed the superoxide anion generation induced by formyl-Met-Leu-Phe (fMLP) or complement-opsonized zymosan and inhibited the phagocytosis of complement-opsonized zymosan or IgG-opsonized latex particles. Furthermore, glucosamine inhibited the release of granule enzyme lysozyme from phagocytosing neutrophils and suppressed neutrophil chemotaxis toward zymosan-activated serum. In addition, glucosamine inhibited fMLP-induced up-regulation of CD11b significantly, polymerization of actin, and phosphorylation of p38 mitogen-activated protein kinase (MAPK). In contrast, N-acetyl-glucosamine, an analogue of glucosamine, did not affect these neutrophil functions (superoxide generation, phagocytosis, granule enzyme release, chemotaxis, CD11b expression, actin polymerization, and p38 MAPK phosphorylation) at the concentrations examined (1-10 mM). Together these observations likely suggest that glucosamine suppresses the neutrophil functions, thereby possibly exhibiting anti-inflammatory actions in arthritis.

Actins↗

PubMed2002

In vivo administration of glucosamine inhibited phosphatidylinositol 3-kinase activity without affecting tyrosine phosphorylation of the insulin receptor or insulin receptor substrate in rat adipocytes.

We examined insulin signaling in rat epididymal adipocytes which developed insulin resistance by the in vivo infusion of glucosamine. Insulin-stimulated 2-deoxyglucose uptake into the adipocytes isolated from rats which were infused glucosamine for 4 hours was diminished by 26%. To analyze insulin signaling in adipocytes, the epididymal fat tissues were harvested 5 minutes after insulin administration (10U/kg), which was administered immediately after glucosamine infusion. Glucosamine had no effect on the insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)-1. Glucosamine infusion decreased insulin-stimulated phosphatidylinositol (PI) 3-kinase activity by 66%. Glucosamine infusion also inhibited insulin-stimulated PI 3-kinase activity associated with IRS-1, 2, 3 by 30%, 43%, and 44%, respectively. There was no difference in the association of the 85kDa subunit of PI 3-kinase with the IRS-1 and IRS-2 protein. PI 3-kinase activity in adipocytes from rats treated with glucosamine that were administered platelet derived growth factor (3microg/kg) for 5 minutes was also reduced by 39%. When we measured the kinase activity of protein kinase C (PKC) lamda, which is the downstream effector of PI 3-kinase in isolated adipocytes, we found that glucosamine inhibited insulin stimulated PKClamda kinase activity by 33%. These results suggest that glucosamine infusion contributes to the development of insulin resistance by mainly modulating the PI 3-kinase molecules.

Adipocytes↗