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PubMed2007

Hemostatic properties of glucosamine-based materials.

Glucosamine- and N-acetyl glucosamine-containing polymers are being used in an increasing number of biomedical applications, including in products for surface (topical) hemostasis. The studies presented here investigate the relationship between the structure (conformation) and function (activation of hemostasis) of glucosamine-based materials. Several polymer systems were studied, including fibers isolated from a microalgal source containing poly-N-acetyl glucosamine polymers that are organized in a parallel, hydrogen-bonded tertiary structure and can be chemically modified to an antiparallel orientation; and gel formulation derivatives of the microalgal fibers consisting of partially deacetylated (F2 gel) and fully deacetylated (F3 gel) polymers. Comparison of the properties of the poly-N-acetyl glucosamine fiber-derived materials with chitin, chitosan, and commercial chitosan-based products are presented. Several studies were performed with the glucosamine-based materials, including (1) an analysis of the ability of materials to activate platelets and turnover of the intrinsic coagulation cascade, (2) an examination of the viscoelastic properties of mixtures of platelet-rich plasma and the glucosamine-based materials via thromboelastography, and (3) scanning electron microscopic studies to examine the morphology of the glucosamine-based materials. The results presented demonstrate that hemostatic responses to the glucosamine-based materials studied are highly dependent on their chemical nature and tertiary/quaternary structure. The unique natural microalgal fibers were found to have strongly prohemostatic activity compared to the other materials studied.

Acetylglucosamine↗

PubMed2002

Lactose-egg yolk diluent supplemented with N-acetyl-D-glucosamine affect acrosome morphology and motility of frozen-thawed boar sperm.

These experiments were carried out to investigate the effect of N-acetyl-D-glucosamine, and to obtain additional information about the effect of orvus es paste (OEP) and egg yolk concentration in the freezing of boar sperm in the maxi-straw. The highest post-thaw acrosomes of normal apical ridge (NAR) and motility were obtained with 0.025 or 0.05% N-acetyl-D-glucosamine concentration in the first diluent. However, there were no effects of N-acetyl-D-glucosamine among the diluents with or without N-acetyl-D-glucosamine at the second dilution. The N-acetyl-D-glucosamine in the first and second diluents was added at room temperatures (20-23 degrees C) and 5 degrees C, respectively. It is suggested that the temperature of N-acetyl-D-glucosamine addition is important for the effect of boar sperm protection during freezing and thawing. When the 0.05% N-acetyl-D-glucosamine was supplemented in the first diluent, the optimum final OEP content was 0.5%. The optimum content of egg yolk in the diluent with 0.05% N-acetyl-D-glucosamine concentration was 20% and egg yolk was one of the main cryoprotective agents. In conclusion, we found out that the diluent with 0.025 or 0.05% soluble N-acetyl-D-glucosamine in the first diluent, 0.5% final orvus es paste concentration and 20% egg yolk concentration significantly enhanced NAR acrosomes and motility of boar sperm after freezing and thawing.

Acetylglucosamine↗

PubMed2003

The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.

BACKGROUND: With increasing use of glucosamine-containing supplements for the treatment of osteoarthritis, there is increasing concern in the medical community about possible toxic effects. The present study was undertaken to determine whether glucosamine supplementation altered hemoglobin A1c concentrations in patients with well-controlled diabetes mellitus. OBJECTIVE: To evaluate possible effects of glucosamine supplementation on glycemic control in a selected population of patients with type 2 diabetes mellitus. DESIGN: Placebo-controlled, double-blinded, randomized clinical trial. SETTING: Outpatient, diabetes monitoring clinic. PATIENTS: Patients were typically elderly patients, evenly divided between men and women. Most of the patients were being treated with 1 or 2 drugs for glycemic control. INTERVENTION: In daily doses for 90 days, patients received either placebo or a combination of 1500 mg of glucosamine hydrochloride with 1200 mg of chondroitin sulfate (Cosamin DS; Nutramax Laboratories Inc, Edgewood, Md). Main Outcome Measure Hemoglobin A1c levels before and after 90 days of therapy. RESULTS: There were 4 withdrawals from the glucosamine-treated group. Three were related to comorbidities (myocardial infarction, congestive heart failure, and atrial fibrillation) and 1 to a possible adverse reaction (excessive flatus). No other patient reported any adverse effects of glucosamine therapy, and no patient had any change in their diabetes management. Mean hemoglobin A1c concentrations were not significantly different between groups prior to glucosamine therapy. Posttreatment hemoglobin A1c concentrations were not significantly different between groups, nor were there any significant differences within groups before and after treatment. CONCLUSION: This study demonstrates that oral glucosamine supplementation does not result in clinically significant alterations in glucose metabolism in patients with type 2 diabetes mellitus.

Aged↗

PubMed2005

Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses.

OBJECTIVE: To examine the concentration of glucosamine in the synovial fluid and its pharmacokinetics in serum in a large animal model following dosing with glucosamine HCl at clinically relevant levels. METHODS: Eight adult female horses were studied. After an overnight fast, glucosamine HCl (20 mg/kg of body weight) was administered by either nasogastric (NG) intubation or intravenous (IV) injection. Blood samples were collected before dosing and at 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes after dosing. Synovial fluid samples were collected from the radiocarpal joints 48 hours before dosing and at 1 and 12 hours after dosing. Glucosamine was assayed by fluorophore-assisted carbohydrate electrophoresis. RESULTS: The maximum concentration of glucosamine in serum reached approximately 300 muM ( approximately 50 microg/ml) following IV dosing and approximately 6 microM (approximately 1 microg/ml) following NG dosing. Synovial fluid concentrations reached 9-15 microM with IV dosing and 0.3-0.7 microM with NG dosing, and remained elevated (range 0.1-0.7 microM) in most animals even at 12 hours after dosing. Following NG dosing, the median serum maximal concentration of 6.1 microM (range 4.38-7.58) was attained between 30 minutes and 4 hours postdose. The mean apparent volume of distribution was 15.4 liters/kg, the mean bioavailability was 5.9%, and the mean elimination half-life was 2.82 hours. CONCLUSION: Clinically relevant dosing of glucosamine HCl in this large monogastric animal model results in serum and synovial fluid concentrations that are at least 500-fold lower than those reported to modify chondrocyte anabolic and catabolic activities in tissue and cell culture experiments. We conclude that the apparent therapeutic benefit of dietary glucosamine on pain and joint space width in humans and animals may be secondary to its effects on nonarticular tissues, such as the intestinal lining, liver, or kidney, since these may be exposed to much high levels of glucosamine following ingestion.

Administration, Oral↗

PubMed2005

Effect of oral glucosamine on cartilage degradation in a rabbit model of osteoarthritis.

OBJECTIVE: To determine whether oral glucosamine alleviates cartilage degradation in an animal model of osteoarthritis (OA). METHODS: The effect of 8 weeks of daily oral glucosamine hydrochloride on degeneration of articular cartilage was evaluated in rabbits in which anterior cruciate ligament transection (ACLT) was performed to induce OA. Animals were treated with glucosamine (n = 16) or a placebo (n = 16) and necropsied at 11 weeks. Seven unoperated rabbits served as controls. The articular cartilage was evaluated macroscopically and histologically and analyzed for total type II collagen and glycosaminoglycan (GAG) content. RESULTS: Histologic analysis revealed that loss of proteoglycan, based on Safranin O-fast green staining, was significantly reduced in the lateral tibial plateau cartilage of ACL-transected limbs in the glucosamine group compared with ACL-transected limbs in the placebo group, with a similar, but not significant, trend for the lateral femoral condylar cartilage. Likewise, macroscopic analysis of cartilage showed that the lateral tibial plateau alone had a significantly lower rate of disease in the glucosamine group, which was consistent with the results of the independent histologic assessment. However, no significant treatment effect was detected when composite histologic scores were analyzed. A significant reduction in GAG content was observed in the femoral condyles of placebo-treated ACL-transected joints, but not in the same region of glucosamine-treated ACL-transected joints, compared with their respective contralateral unoperated joints. CONCLUSION: Oral administration of glucosamine had a detectable, site-specific, partial disease-modifying effect in this model of OA. From a clinical perspective, the administration of glucosamine did not prevent fibrillation and/or erosions of the articular cartilage in all of the treated animals, and no effects were detected in the medial joint compartments.

Administration, Oral↗

PubMed2000

Glucosamine inhibits inducible nitric oxide synthesis.

Glucosamine is widely used in Europe for treatment of arthritis in humans. Based on recent findings that excess production of nitric oxide (NO) by inducible NO synthase (iNOS) mediates the pathogenesis of arthritis, we hypothesized that glucosamine may inhibit NO synthesis. To test this hypothesis, we used an in vivo rat model of lipopolysaccharide (LPS)-induced inflammation. Intravenous administration of d-glucosamine (0.5 mmol/kg) 6 h before, at the time of, and 6 h after intraperitoneal LPS injection (1 mg/kg) decreased urinary excretion of nitrate by 31 and 48%, respectively, at days 1 and 2 post LPS administration. When cultured macrophages were treated with LPS (1 microg/ml) to induce iNOS expression, addition of 0.1, 0.5, 1, and 2 mM d-glucosamine decreased NO production by 18, 38, 60, and 89%, respectively. Glucosamine had no effect on cellular arginine, NADPH or tetrahydrobiopterin concentrations, but dose-dependently suppressed iNOS protein expression. Similar decreases in iNOS protein occurred in spleen, lung, and peritoneal macrophages of glucosamine-treated rats. These studies demonstrate that glucosamine is a novel inhibitor of inducible NO synthesis via inhibition of iNOS protein expression, and provide a biochemical basis for the use of glucosamine in treating chronic inflammatory diseases such as arthritis.

Animals↗

PubMed1977

An evaluation of D-glucosamine as a gratuitous catabolite repressor of Saccharomyces carlsbergensis.

Glucose represses mitochondrial biogenesis and the fermentation of maltose, galactose and sucrose in yeast. We have analyzed the effect of D-glucosamine on these functions in order to determine if it can produce a similar repression. It was found that glucosamine represses the respiration rate (QO2) but more rapidly than glucose and to a final level slightly higher than in glucose-treated cells. Derepression of the respiration rate following either glucose or glucosamine repression was similar. A two hour lag was followed by a linear increase in QO2 to the derepressed level. Both glucose and glucosamine repressed the level of cytochrome oxidase to the same level. Glucosamine was also found to repress maltose and galactose fermentation but not sucrose fermentation. The derepression of maltase synthesis was inhibited by glucosamine. The constitutive synthesis of maltase was repressed by the addition of glucosamine. Glucosamine was judged to produce a repressed state similar to glucose repression in many respects.

Electron Transport Complex IV↗

PubMed2005

Preventive actions of a high dose of glucosamine on adjuvant arthritis in rats.

OBJECTIVE: Glucosamine, a naturally occurring amino monosaccharide has been used to treat or prevent osteoarthritis in humans. In this study, we evaluated the effect of glucosamine on rat adjuvant arthritis, a model of rheumatoid arthritis. MATERIALS AND METHODS: Adjuvant arthritis was induced in male Wistar rats by injection of Freund's complete adjuvant (FCA) into the right hind paw, and 300 mg/kg of glucosamine, an extra-dose compared with a regular dose for osteoarthritis patients (1.5 g/day, approximately 25 mg/kg), was orally administered once a day to the arthritic rats for 22 days. RESULTS: Glucosamine significantly suppressed the increase in arthritis score (p < 0.05) after day 10 of adjuvant injection, and inhibited the swelling of FCA-injected right and -uninjected left hind paws (p < 0.01) after day 18. In addition, histopathological examination of the arthritic joints revealed that glucosamine suppressed synovial hyperplasia, cartilage destruction and inflammatory cell infiltration. Furthermore, glucosamine reduced the production of nitric oxide and prostaglandin E(2) in plasma (p < 0.05). CONCLUSIONS: These observations suggest that glucosamine is able to suppress the progression of adjuvant arthritis in rats. Glucosamine may be expected as a novel anti-inflammatory agent for treatment of rheumatoid arthritis.

Animals↗

PubMed2001

Presence of glutamine:fructose-6-phosphate amidotransferase for glucosamine-6-phosphate synthesis in endothelial cells: effects of hyperglycaemia and glutamine.

AIMS/HYPOTHESIS: Recent studies show that glucosamine infusion impairs endothelium-dependent blood flow in normoglycaemic rats. The pathophysiological relevance of this finding, however, depends on whether de novo glucosamine synthesis occurs in endothelial cells. The aim of this study was to test the hypothesis of whether glutamine:fructose-6-phosphate amidotransferase (the first and key regulatory enzyme in hexosamine synthesis) is present for endothelial glucosamine synthesis. METHODS: Bovine venular, bovine aortic, human microvascular, human umbilical vein, and rat coronary microvascular endothelial cells were used to measure glutamine:fructose-6-phosphate amidotransferase activity. To determine glucosamine-6-phosphate synthesis in intact cells, they were incubated for 1 h in Krebs bicarbonate buffer containing 5, 15 or 30 mmol/l [U-14C]glucose and 0.5, 2 or 4 mmol/l glutamine. The [14C]Glucosamine-6-phosphate and its end products ([14C]UDP-N-acetylglucosamine and [14C]UDP-Nacetylgalactosamine) were separated by HPLC. RESULTS: There were high glutamine:fructose-6-phosphate amidotransferase activities in all endothelial cells studied. Exposure of cells to 15 to 30 mmol/l glucose or 2 to 4 mmol/l glutamine increased enzyme activity. Glucosamine-6-phosphate, UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine syntheses increased with increasing extracellular concentrations of glucose from 5 to 30 mmol/l or of glutamine from 0.5 to 4 mmol/l. CONCLUSION/INTERPRETATION: Our results show the presence of glutamine:fructose-6-phosphate amidotransferase for de novo glucosamine synthesis in endothelial cells and the modulation of this pathway by hyperglycaemia and glutamine. As glucosamine inhibits endothelial nitric oxide synthesis, these findings could have important implications for impaired endothelium-dependent relaxation and vascular dysfunction in diabetes mellitus.

Animals↗

PubMed2006

Directed evolution and characterization of Escherichia coli glucosamine synthase.

Glucosamine synthase (GlmS) converts fructose-6-phosphate to glucosamine-6-phosphate. Overexpression of GlmS in Escherichia coli increased synthesis of glucosamine-6-P, which was dephosphorylated and secreted as glucosamine into the growth medium. The E. coli glmS gene was improved through error-prone polymerase chain reaction (PCR) in order to develop microbial strains for fermentation production of glucosamine. Mutants producing higher levels of glucosamine were identified by a plate cross-feeding assay and confirmed in shake flask cultures. Over 10 mutants were characterized and all showed significantly reduced sensitivity to inhibition by glucosamine-6-phosphate. Ki of mutants ranged from 1.4 to 4.0 mM as compared to 0.56 mM for the wild type enzyme. Product resistance resulted from single mutations (L468P, G471S) and/or combinations of mutations in the sugar isomerase domain. Most overexpressed GlmS protein was found in the form of inclusion bodies. Cell lysate from mutant 2123-72 contained twice as much soluble GlmS protein and enzyme activity as the strain overexpressing the wild type gene. Using the product-resistant mutant, glucosamine production was increased 60-fold.

Acetylglucosamine↗

PubMed2006

Development and validation of a sensitive HPLC-ESI-MS/MS method for the direct determination of glucosamine in human plasma.

A sensitive and specific HPLC-ESI-MS/MS method for the direct determination of glucosamine in human plasma has been developed and validated. Plasma samples were analyzed after a simple, one-step protein precipitation clean-up with trichloroacetic acid using a polymer-based amino high-performance liquid chromatography (HPLC) column and a water/acetonitrile mobile phase elution gradient, with d-[1-(13)C]glucosamine as the internal standard. Detection was performed by mass spectrometry, using an electrospray source and employing multiple reaction monitoring to separately monitor glucosamine and the internal standard. The limit of quantification of the method was 10ng/ml of glucosamine and the calibration curve showed a good linearity up to 1000ng/ml. The precision (R.S.D.) and the accuracy (bias) of the method at the limit of quantification were 13.8 and 4.0%, respectively, and the mean recovery of glucosamine at three concentration levels was 101.6+/-5.7%. The method was applied for the determination of glucosamine concentrations in human plasma samples collected from untreated healthy volunteers and, in a separate bioavailability study, to evaluate plasma glucosamine pharmacokinetics profiles after oral administration of crystalline glucosamine sulfate.

Biological Availability↗

PubMed2002

A survey of self-medication practices and perceived effectiveness of glucosamine products among older adults.

OBJECTIVES: The purpose of this study was to investigate the decision-making and self-treatment practices of older users of glucosamine products, namely (1) how do older adults decide to use glucosamine products? (2) what influences their choice? (3) how do they manage their glucosamine treatment? and (4) what is their perception of the effectiveness, side effects, and costs of glucosamine products? DESIGN: A descriptive, exploratory study using a questionnaire survey. SETTING: Province-wide. Invitations to participate were extended to all people living in a Canadian province who used/had used glucosamine products. RESULTS: Advice from friends was a major factor in the decision to take glucosamine. Cost was a major factor influencing the type and brand name of the product used. Ninety-two percent managed their own treatment. The majority (88%) used glucosamine regularly; only one-third took the recommended daily dose. Sixty-seven percent perceived the product to be helpful in relieving symptoms. CONCLUSION: Public education and further research is needed regarding the use of glucosamine products.

Aged↗

PubMed2001

Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia.

OBJECTIVE: To assess the crossreactivity of glucosamine sulfate, used for treatment of degenerative joint disease with antibodies induced in heparin-induced thrombocytopenia (HIT). BACKGROUND: HIT is a severe adverse effect of heparin therapy induced by an immunological mechanism. The antibodies in HIT are induced by a complex of heparin and, in most cases, platelet factor 4. Hereby generation of the antigen is not strictly dependent on heparin. Heparin can be substituted by a variety of polysulfated carbohydrates. In vitro and in vivo crossreactivity of HIT antibodies has been demonstrated for a chemically polysulfated chondroitin-like substance (Arteparon, Luitpoldwerke, Munich, Germany), formerly used for chondroprotection. Another drug widely used in the treatment of degenerative joint disease is glucosamine sulfate. Glucosamine is a building block of glycosaminoglycans, of which heparin is the clinically most important. Many patients with degenerative joint disease use glucosamine sulfate. This group is also at the highest risk to develop HIT following joint replacement surgery. METHODS: We examined the interactions of glucosamine sulfate (DONA 200-S, Opfermann, Wiehl, Germany) with platelets and antibodies of patients with HIT in and without the presence of heparin. Sera of 5 HIT patients and platelets of 4 healthy donors were used. The binding of HIT antibodies to PF4/glucosamine sulfate complexes was assessed by an ELISA. RESULTS: HIT antibodies did not activate platelets in the presence of glucosamine sulfate in a serotonin-release assay. Preincubation with glucosamine sulfate did not inhibit platelet activation by HIT antibodies in the presence of heparin (0.2 IU/ml). Antibodies bonded to PF4/heparin but not to PF4/glucosamine sulfate complexes. CONCLUSIONS: In contrast to sulfated glycosaminoglycans, there is no evidence for an immunological crossreactivity of HIT antibodies between heparin and glucosamine sulfate.

Antibody Specificity↗

PubMed1979

Incorporation of N-fluoroacetyl-D-glucosamine into hyaluronate by rabbit tracheal explants in organ culture.

1. Incubation of rabbit tracheal explants with N-[(3)H]acetyl-d-glucosamine and N-acetyl-d-[1-(14)C]glucosamine led to labelling of a number of soluble macromolecular products separable from the medium, after papain digestion, by ion-exchange chromatography. 2. With N-acetyl-d-[1-(14)C]glucosamine in the incubation medium, a neutral glycoprotein, two acidic glycoprotein fractions, hyaluronic acid and a glycosaminoglycan fraction were obtained and all were radioactively labelled. Similar labelling occurred with N-fluoroacetyl-d-[1-(14)C]glucosamine or N-fluoro[(3)H]acetylglucosamine as precursor. 3. Maximal labelling was obtained at 96h after incubation of cultures. N-Fluoroacetyl-glucosamine under these conditions was incorporated into hyaluronate less efficiently than N-acetylglucosamine. 4. With N-fluoroacetyl-d-[1-(14)C]glucosamine as precursor, a hyaluronate component was separated that on enzymic degradation by glycosidases (hyaluronidase, beta-glucuronidase and N-acetyl-beta-hexosaminidase) yielded a (14)C-labelled oligosaccharide fraction together with N-acetyl-d-[1-(14)C]glucosamine and N-fluoroacetyl-d-[1-(14)C]glucosamine, consistent with some exchange of N-acetyl groups having occurred. 5. The results on enzymic degradation of labelled macromolecules by glycosidases suggest that the presence of incorporated N-fluoroacetyl side chains may render the hyaluronate analogue more resistant to hyaluronidase.

Acetylglucosamine↗

PubMed1998

Glucosamine-induced insulin resistance in 3T3-L1 adipocytes is caused by depletion of intracellular ATP.

Glucosamine, which enters the hexosamine pathway downstream of the rate-limiting step, has been routinely used to mimic the insulin resistance caused by high glucose and insulin. We investigated the effect of glucosamine on insulin-stimulated glucose transport in 3T3-L1 adipocytes. The Delta-insulin (insulin-stimulated minus basal) value for 2-deoxyglucose uptake was dramatically inhibited with increasing concentrations of glucosamine with an ED50 of 1.95 mM. Subcellular fractionation experiments demonstrated that reduction in insulin-stimulated 2-deoxyglucose uptake by glucosamine was due to an inhibition of translocation of both Glut 1 and Glut 4 from the low density microsomes (LDM) to the plasma membrane. Analysis of the insulin signaling cascade revealed that glucosamine impaired insulin receptor autophosphorylation, insulin receptor substrate (IRS-1) phosphorylation, IRS-1-associated PI 3-kinase activity in the LDM, and AKT-1 activation by insulin. Measurement of intracellular ATP demonstrated that the effects of glucosamine were highly correlated with its ability to reduce ATP levels. Reduction of intracellular ATP using azide inhibited Glut 1 and Glut 4 translocation from the LDM to the plasma membrane, insulin receptor autophosphorylation, and IRS-1 tyrosine phosphorylation. Additionally, both the reduction in intracellular ATP and the effects on insulin action caused by glucosamine could be prevented by the addition of inosine, which served as an alternative energy source in the medium. We conclude that direct administration of glucosamine can rapidly lower cellular ATP levels and affect insulin action in fat cells by mechanisms independent of increased intracellular UDP-N-acetylhexosamines and that increased metabolism of glucose via the hexosamine pathway may not represent the mechanism of glucose toxicity in fat cells.

3T3 Cells↗

PubMed1977

Regulation of glucosamine utilization in Staphylococcus aureus and Escherichia coli.

Glucosamine- or N-acetylglucosamine-requiring mutants of Staphylococcus aureus 209P and Escherichia coli K12, which lack glucosamine-6-phosphate synthetase [2-amino-2-deoxy-D-glucose-6-phosphate ketol-isomerase (amino-transferring); EC 5.3.1.19], were isolated. Growth of these mutants on glucosamine was inhibited by glucose, but growth on N-acetylglucosamine was not. Addition of glucose to mutant cultures growing exponentially on glucosamine inhibited growth and caused death of bacteria, though chloramphenicol prevented death. Uptake of glucosamine by S. aureus and E. coli mutants was severely inhibited by glucose whereas uptake of N-acetylglucosamine was only slightly inhibited. Uptake of glucose was not inhibited by either glucosamine or N-acetylglucosamine. In glucosamine auxotrophs, glucose causes glucosamine deficiency which interrupts cell wall synthesis and results in some loss of viability in the presence of continued protein synthesis.

Acetylglucosamine↗

PubMed2003

Glucosamine and glucose induce insulin resistance by different mechanisms in rat skeletal muscle.

It has been hypothesized that glucose-induced insulin resistance is mediated by accumulation of UDP-N-acetylhexosamines (UDP-HexNAcs). In a previous study on rat epitrochlearis muscles incubated with high concentrations of glucose and insulin (Kawanaka K, D-H Han, J Gao, LA Nolte, and JO Holloszy. J Biol Chem 276: 20101-20107, 2001), we found that insulin resistance developed even when the increase in UDP-Hex-NAcs was prevented. Furthermore, actinomycin D completely prevented glucose-induced insulin resistance despite a greater accumulation of UDP-HexNAcs. In the present study, we used the same epitrochlearis muscle preparation, as well as the rat hemidiaphragm, to determine whether, like glucose, glucosamine causes insulin resistance by an actinomycin D-inhibitable process. Incubation of diaphragm muscles with 10 mM glucosamine for 3 h resulted in an approximately fivefold increase in UDP-HexNAcs, an approximately 50% reduction in insulin responsiveness of glucose transport, and a 58% reduction in ATP concentration. These effects of glucosamine were not prevented by actinomycin D. Incubation of epitrochlearis muscles with 20 mM glucosamine for 3 h or with 10 mM glucosamine for 5 h also caused large decreases in insulin responsiveness of glucose transport but with no reduction in ATP concentration. Actinomycin D did not prevent the glucosamine-induced insulin resistance. The insulin-induced increases in tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the binding of PI 3-kinase to IRS-1 were decreased approximately 60% in epitrochlearis muscles exposed to glucosamine. This is in contrast to glucose-induced insulin resistance, which was not associated with impaired insulin signaling. These results provide evidence that glucosamine and glucose induce insulin resistance by different mechanisms.

Adenosine Triphosphate↗

PubMed1998

Glucosamine sulfate for osteoarthritis.

OBJECTIVE: To characterize the usefulness of glucosamine sulfate in the treatment of patients with osteoarthritis (OA). DATA SOURCES AND STUDY SELECTION: Pertinent citations were identified via a MEDLINE search (January 1975-March 1997). Only trials available in the English language involving human subjects, OA, and glucosamine sulfate were selected for review. DATA SYNTHESIS: OA is the most common form of arthritis and represents a major cause of morbidity and disability in the elderly. The main symptom of OA is pain and most of the commonly prescribed medications (e.g. acetaminophen, nonsteroidal antiinflammatory drugs) have been targeted at relieving the pain. Some of these medications have serious adverse effects and do not necessarily change the natural course of the disease. Glucosamine sulfate, a nutritional supplement, has recently emerged as an alternative treatment option for patients with OA. The beneficial effects of this chondroprotective agent have been reported to reverse or at least stop the progression of the disease without inducing serious adverse effects. Limited data from short-term human trials suggest that glucosamine sulfate administered orally, intravenously, intramuscularly, and intraarticularly may produce a gradual and progressive reduction in joint pain and tenderness, as well as improved range of motion and walking speed. Results of the trials have also shown that glucosamine has produced consistent benefits (> 50% overall improvement in symptom scores) in patients with OA and that, in some cases, it may be equal or superior to ibuprofen in controlling symptoms. CONCLUSIONS: There is evidence that glucosamine sulfate may provide pain relief, reduce tenderness, and improve mobility in patients with OA. Most of the current data, however, are derived from the European and Asian literature and there are no studies supporting the use of this agent in the US. The studies published to date have been done in small numbers of patients; adequate long-term trials examining the safety, efficacy, and optimal dosage requirements of glucosamine sulfate are lacking. Most of the available clinical data are difficult to interpret due to serious deficiencies in study design. Furthermore, studies evaluating the appropriate place of glucosamine sulfate in the therapeutic armamentarium of OA remain to be done.

Anti-Inflammatory Agents, Non-Steroidal↗