Injection Of Glucosamine Research Articles

Efficacy and safety of combining ginkgolide diterpene glucosamine injection with dual antibodies in elderly patients with acute ischemic stroke

Purpose: To investigate the clinical effects and safety of ginkgo biloba diterpene lactone glucosamine injection, combined with dual antibiotic therapy for acute ischemic stroke in elderly individuals within a hyper thrombolytic time window. 
 Methods: 100 elderly patients with acute ischemic stroke at Changsha First Hospital, Changsha, China from March 2022 to March 2023 were randomly and equally assigned to study and control groups (50 patients each). Study group received aspirin and clopidogrel, while control group received ginkgo biloba diterpene lactone glucosamine injection along with dual antibodies. Clinical efficacy, National Institutes of Health Stroke Scale (NIHSS) score, Instrumental Activities of Daily Living (IADL) score, cerebral hemodynamics, and safety were compared between the two groups. 
 Results: There was no significant difference in effective rate between the two groups (p > 0.05). However, following treatment, study group showed superior NIHSS and IADL scores compared to control group, with greater statistical significance as the disease progressed. Doppler ultrasound revealed that study group had smaller Pulsatility index (PI) values and larger mean cerebral artery blood flow velocity (Vm), and systolic value (Vs) compared to control group (p < 0.05). In study group, three adverse reactions were reported (gastrointestinal discomfort, abnormal liver/kidney function, and skin itching), whereas the control group experienced five adverse reactions (gastrointestinal discomfort, abnormal liver/kidney function, dizziness, and skin itching). 
 Conclusion: The combination of Ginkgo biloba diterpene lactone glucosamine injection and dual antibodies in elderly individuals with acute ischemic stroke within a super thrombolytic time window enhances intracerebral blood flow levels, effectively promotes neurological recovery, improves daily living abilities, and safety. Further research is needed to elucidate the exact pathways involved.

Glucosamine Enhancement of BDNF Expression and Animal Cognitive Function.

Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity; the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway.

Glucosamine regulation of fibroblast growth factor 21 expression in liver and adipose tissues

Obesity is associated with metabolic disorders. Fibroblast growth factor 21 (FGF21) has been recognized as important in metabolism. Glucosamine (GLN) has been demonstrated to perform diverse beneficial functions. This study aimed to reveal whether and how GLN would modulate FGF21 production in relation to metabolism. With in vivo model of normal diet (ND) and high-fat diet (HFD) mice receiving GLN injection and in vitro model of mouse AML12 liver cells and differentiated 3T3L1 adipocytes challenged with GLN, GLN appeared to improve the glucose metabolism in HFD and ND mice and to elevate FGF21 protein expression in HFD liver and to increase both FGF21 protein and mRNA levels in WAT from HFD and ND mice and it also upregulated FGF21 expression in both AML12 and differentiated 3T3L1 cells. By using inhibitors against various signaling pathways, p38, Akt, NF-κB, and PKA appeared potentially involved in GLN-mediated FGF21 production in AML12 cells; GLN was able to mediate activation of NF-κB, p38 or PKA/CREB signaling. Our accumulated findings suggest that GLN may potentially improve the metabolic performance by inducing FGF21 production in liver and adipose tissues and such induction in liver cells may act in part due to GLN induction of the NF-κB, p38 and PKA pathways.

Role of glucosamine in development of diabetic neuropathy independent of the aldose reductase pathway.

Long-term metabolic aberrations contribute to the development of diabetic neuropathy but the precise mechanism or mechanisms remains elusive. We have previously shown that aldose reductase-deficient mice exhibit delayed onset and progression of neuropathy following induction of diabetes, suggesting a role both for downstream metabolites of this enzyme and also for other unrelated pathways. In this study, we have utilized comprehensive metabolomics analyses to identify potential neurotoxic metabolites in nerve of diabetic mice and explored the mechanism of peripheral nerve injury. Aldose reductase knockout and control C57Bl/6J mice were made diabetic by injection of streptozotocin and followed for 8–16 weeks. Diabetic aldose reductase knockout mice exhibited delayed onset of nerve conduction slowing compared to diabetic wild-type mice. The sciatic nerves from aldose reductase knockout mice exposed to 12 weeks of diabetes were used for metabolomics analysis and compared with analyses of nerves from age-matched diabetic wild-type mice as well as non-diabetic aldose reductase knockout and wild-type mice. Neurotoxicity of candidate metabolites was evaluated using cultured Schwann cells and dorsal root ganglion neurons, and further confirmed in vivo. Metabolomics analysis identified elevated glucosamine levels in both diabetic aldose reductase knockout and diabetic wild mice. Exposure to glucosamine reduced survival of cultured Schwann cells and neurons accompanied by increased expression of cleaved caspase 3, CCAT-enhancer-binding homologous protein and mitochondrial hexokinase-I, along with ATP depletion. These changes were suppressed by siRNA to hexokinase-I or the ATP donor, inosine, but not by the antioxidant N-acetylcysteine or the endoplasmic reticulum-stress inhibitor 4-phenylbutyrate. The O-GlcNAcylation enhancer, O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenylcarbamate, did not augment glucosamine neurotoxicity. Single dose glucosamine injection into mice caused a reduction of sciatic nerve Na, K-ATPase activity, ATP content and augmented expression of hexokinase-I, which were suppressed by pretreatment with inosine but not with 4-phenylbutyrate. Mice implanted with a subcutaneous pump to infuse glucosamine for 12 weeks developed nerve conduction slowing and intraepidermal nerve fibre loss, recapitulating prominent indices of diabetic neuropathy. While acute glucosamine neurotoxicity is unlikely to contribute substantially to the slowly developing neuropathy phenotype in humans, sustained energy deprivation induced by glucosamine may well contribute to the pathogenesis of diabetic neuropathy. Our data thus identifies a novel pathway for diabetic neuropathy that may offer a potential new therapeutic target.

Role of O-GlcNAcylation and endoplasmic reticulum stress on obesity and insulin resistance

Abstract Background Obesity is a global public health problem. Obesity closely associated with various metabolic diseases such as; insulin resistance, hypertension, dyslipidemia and cardiovascular diseases. Endoplasmic reticulum (ER) stress is a critical factor for insulin resistance. O-linked N-acetyl-glucosamine (O-GlcNAc); is the post-translational modification which is has a vital role in biological processes; including cell signaling, in response to nutrients, stress and other extracellular stimuli. Materials and methods In this study, we aimed to investigate the role of O-GlcNAc modification in the context of obesity and obesity-associated insulin resistance in adipose tissue. For this purpose, first, the visceral and epididymal adipose tissues of obese and insulin resistant C57BL/6 Lepob/Lepob and wild-type mice were used to determine the O-GlcNAc modification pattern by western blot. Secondly, the external stimulation of O-GlcNAc modification in wild-type mice achieved by intraperitoneal 5 mg/kg/day glucosamine injection every 24 h for 5 days. The effect of increased O-GlcNAc modification on insulin resistance and ER stress investigated in adipose tissues of glucosamine challenged wild-type mice through regulation of the insulin signaling pathway and unfolded protein response (UPR) elements by western blot. In addition to that, the O-GlcNAc status of the insulin receptor substrate-1 (IRS1) investigated in epididymal and visceral adipose tissues of ob/ob, wild-type and glucosamine challenged mice by immunoprecipitation. Results We found that reduced O-GlcNAc levels in visceral and epididymal adipose tissues of obese and insulin-resistant ob/ob mice, although interestingly we observed that increased O-GlcNAc modification in glucosamine challenged wild-type mice resulted in insulin resistance and ER stress. Furthermore, we demonstrated that the IRS1 was modified with O-GlcNAc in visceral and epididymal adipose tissues in both ob/ob mice and glucosamine-injected mice, and was compatible with the serine phosphorylation of this modification. Conclusion Our results suggest that O-GlcNAcylation of proteins is a crucial factor for intracellular trafficking regulates insulin receptor signaling and UPR depending on the cellular state of insulin resistance.

0307 : Acute activation of the hexosamine biosynthetic pathway promotes electrical instability

The hexosamine biosynthetic pathway (HBP) is heightened in cardiomyopathies. We aimed at understanding how over-activation of HBP impacts on cardiac electrophysiology, and acts as a trigger or a substrate of cardiac arrhythmias. Overactivation of the HBP by injection of glucosamine (GlcN 270mg/kg) was assessed under basal conditions and during beta-adrenergic stress on the myocardial energetic status (phosphocreatine to ATP ratio) of rats by 31 P nuclear magnetic resonance spectroscopy. Rat hearts were perfused ex vivo to evaluate the effects of the HBP activation (physiologically: glutamine 0.5mM – gln; overactivated: GlcN 1mM) on: cardiac function, MVO 2 , and arrhythmia score (AS) under basal (spontaneous arrhythmias: sAS) and pacing (pAS) conditions. At the cellular level (HL1 cells), HBP overactivation (GlcN) was assessed on conduction velocity characterized by micro-electrode arrays recordings, and properties of voltage gated ionic channels involved in cellular excitability and conduction by patch clamp experiments. In vivo GlcN did not modify PCr/ATP of the left ventricle under basal conditions. This ratio was significantly decreased during beta-adrenergic stress, while a similar increased heart rate was reported. When hearts were isolated and perfused ex vivo , GlcN induced a decrease of the heart rate and MVO 2 temporarily, and an increase of the sAS and pAS. Physiological activation of HBP with gln did not impact the ex vivo cardiac function and the sAS, but further increased the probability of atrial arrhythmias during pacing. In HL1 cells, GlcN reduced the rate of spontaneous depolarization, modified the direction and the velocity of the impulse propagation, and altered activation and inactivation properties of the sodium channel. Acute HBP activation is associated with an increased vulnerability for arrhythmias and alteration of impulse conduction, suggesting its potential role in the atrial and ventricular arrhythmias. The author hereby declares no conflict of interest

Collagen and glycosaminoglycan synthesis of injured gastrocnemius muscle in rat.

The synthesis of collagen and glycosaminoglycans in a partially ruptured gastrocnemius muscle were studied in 30 rats by giving a single 3H-labelled proline and 14C-labelled glucosamine injection intraperitoneally 2-21 days after a standard transverse contusion injury induced to the left calf of the animals. Both injured and contralateral uninjured gastrocnemius muscles were cut into four analogous 5-mm thick transverse pieces using the center of injury as a site for the middle incision in the injured muscle. The muscle slices were homogenized, dialyzed and then burned in a sample oxidizer which automatically divides the two radioisotopes into two different sample flasks. The radioactivities were measured using a liquid scintillation spectrometer. The content of glycosaminoglycans within the site of injury increased to a maximum 5 days after trauma, and decreased in amount thereafter. The uptake of 3H-proline indicating the synthesis of collagen was very low 5 days after trauma but increased to a maximum between the 10th and 14th day; more intensively in the proximal border of the injury than in the distal one. The uptake decreased again in amount 21 days after trauma. Burning of an in vivo radioactively labelled sample in a sample oxidizer provides a simple method in determination of the two radioactive isotopes as indicators of two main components of granulation and scar tissue.

Metabolism of glucosamine in the liver of Scyliorhinus canicula (selachian)

(1) The metabolism of the glucosamine was studied in the liver of S. canicula, after injection of D-(1-14C) glucosamine into the animal. (2) The labelled acid-soluble derivatives were separated by ion exchange columns and characterized by chromatography and electrophoresis, and were identified as glucosamine, glucosamine 6-P, N-acetylglucosamine, N-acetylmannosamine, N-acetylneuraminic acid, N-acetylglucosamine 6-P, N-acetylglucosamine 1-P, N-acetylmannosamine 6-P, UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine. (3) The variation with time after glucosamine injection of the radioactivity of the fractions separated on Dowex 1-X4 was investigated. This study showed a decrease of the radioactivity in the fraction 1 (glucosamine and glucosamine 6-P), an increase in the fraction II (N-acetylneuraminic acid) and the fraction IV (UDP-N-acetylhexosamines), and a stability in the fraction III (phosphorylated N-acetylhexosamines). (4) The absence of label in neutral hexoses and their phosphorylated derivatives was interpretated as due to the weak activity of the glucosamine 6-P isomerase, which is positively modulated by the N-acetylglucosamine 6-P.

The matrix of the optic vesicle-presumptive lens interface during induction of the lens in the chicken embryo

The cell coats of the presumptive lens cells and the extracellular interface between the lens rudiment and optic vesicle were investigated in the chicken embryo throughout the period during which lens induction is presumed to take place. Histochemical methods showed that the cell coats contained both glycoproteins and glycosaminoglycans. Autoradiography after [3H]glucosamine injection indicated incorporation of the precursor with subsequent localization primarily at the cell surface. No obvious changes in the properties of the coat were noted with the progression of early lens morphogenesis. The extracellular matrix at the interface between ectoderm and optic vesicle also contained glycoprotein and glycosaminoglycan. There was a heavy concentration of [3H]glucosamine-containing macromolecules in the area. Electron microscopy revealed that the interface consisted of the basement membrane systems of lens and optic vesicle, fused with their external fibrillar layers. In contrast to the findings on cell coats the density of the interfacial matrix increases appreciably during the lens induction period. Evidence suggests that the cells of the two ocular epithelia are themselves the source of the matrix materials. It is proposed that the macromolecules excreted by the epithelial cells into the interface interact at different concentrations to form aggregates of various structure by a process of self-assembly. This may be reflected in the different ultrastructure of the layers of the interfacial matrix. Quantitative changes in the density of the matrix, leading to increased adhesion between lens rudiment and optic vesicle, may restrict the lateral spreading of the lens cells and so fix the basal area of the lens rudiment. This, together with continued cell replication, may produce the cell crowding, placode formation and invagination characteristic of lens morphogenesis.

Transfer of radioactive material between electrically coupled neurons of the leech central nervous system

Intracellular application of tritiated precursors by means of microiontophoresis was performed on nerve cells in isolated segmental ganglia of the leech ventral nerve cord. Incorporation as well as intra- and interneuronal transport were studied by autoradiography after injection of fucose, glucosamine, glycine, leucine, orotic acid and uridine. Within several minutes of intraneuronal injection the precursors were incorporated into macromolecules. Depending upon the tracer used, the radioactive material was distributed in a specific pattern over the cell somata and then released into the nerve processes. After application of orotic acid and uridine a transport of radioactive material, presumably RNA, could be observed in the processes of the injected neurons at a distance of about 200–500 μm. Fucose and glucosamine injection resulted in the most extended labeling of the nerve cell processes, indicating a transport rate of about 11 mm/day. When the radiochemicals were injected into one of the two electrically coupled giant nerve cells — the so-called Retzius cells (Rc) — a specific labeling not only of the injected Rc but also of the coupled but not injected Rc was found. Injection of protein or glycoprotein precursors into one Rc produced heavy labeling of both Rcs including their processes; a slight labeling of other ganglion compartments was only found after increasing the dosage of the amino acids glycine and leucine. With orotic acid and uridine this interneuronal transfer was confined to the electrically coupled Rc twin. Intracellular injection of one Rc with puromycin followed by injection of amino acids or fucose into the same Rc or into the coupled Rc resulted in an inhibition of precursor incorporation within the puromycin-injected Rc and an exclusive labeling of the coupled Rc, thus indicating that the precursors themselves were transferred. It is suggested that after microiontophoretic application an interneuronal transfer of relatively low molecular weight material takes place, probably across the low-resistance junction through which the Rcs are electrically coupled.

Studies on bone matrix glycoproteins. Incorporation of (1-14C)glucosamine and plasma (14C)glycoprotein into rabbit cortical bone.

The radioactively labelled constituents present in bone matrix were compared 12 days after injection of either [(14)C]glucosamine or plasma [(14)C]glycoprotein. Both precursors are utilized in the synthesis of organic matrix by bone tissue. Cortical bone from animals injected with [(14)C]glucosamine contains radioactivity derived from glucosamine and plasma glycoproteins and all glycoprotein fractions are labelled. Plasma [(14)C]glycoprotein labels the less acidic glycoproteins to a greater extent than the more acidic components. An antibody has been raised against the less-acidic-glycoprotein fraction of bone. The latter contains a glycoprotein of alpha-mobility that appears to be concentrated specifically in bone tissue and which is present also in plasma. This alpha-glycoprotein accounts for a large proportion of the components labelled and retained in bone matrix after [(14)C]glucosamine injection.

Specific repression of a puff in the salivary gland chromosomes of Drosophila virilis after injection of glucosamine.

Five hours after the injection of glucosamine into the hemolymph of Drosophila virilis larvae, puff 55E in the salivary gland chromosomes is significantly reduced in its activity. This observation in connection with the circumstances under which the activity of puff 55E decreases during normal development led to the proposition that its activity is involved in mucoprotein synthesis in the salivary glands during the third larval instar. Factors that may regulate the activity of puff 55E are discussed.

Inactivation and resynthesis of glucosamine-6-phosphate synthetase after treatment with glutamine analogs

The biosynthesis of D-glucosamine-6-phosphate by l-Glutamine: d-fructose-6-phosphate aminotransferase in the liver of the rat is irreversibly inactivated by injection of N-acetyl-6-diazo-5-oxo- l-norleucine, Duazomycin A. The course of inactivation parallels the disappearance of UDP-N-acetyl-hexosamine from the liver. Injection of glucosamine with Duazomycin A completely protects the enzyme against inactivation, without protecting enzymes involved in the biosynthesis of purine and cytosine nucleotides that are sensitive to Duazomycin A. The injection of glucosamine either 2 or 4 hr after Duazomycin A reduces the lag in appearance of aminotransferase activity without altering the ultimate rate of what appears to be resynthesis, since the process is inhibited by puromycin and dl-ethionine; the time required to regain 50% of the activity is 13 to 20 hr. Crude and partially purified extracts containing the aminotransferase are irreversibly inactivated by either Duazomycin A or 6-diazo-5-oxo- l-norleucine; the rate of inactivation by the latter is dependent upon its concentration over the range 1 × 10 −6 to 3 × 10 −4 m (K m = 8 × 10 −5 m ) . Both l-glutamine and UDP-N-acetylglucosamine reduce the rate of inactivation of the enzyme by 6-diazo-5-oxo- l-norleucine in vitro; a combination of both compounds is more effective than either alone, and evidence is presented that the two protective compounds act at different sites on the enzyme. The protective effects have been demonstrated in a crude extract and with a partially purified enzyme. Glucose-6-phosphate, fructose-6-phosphate and other amino sugars and nucleotide compounds related to UDP-N-acetyl-glucosamine do not protect against inactivation by 6-diazo-5-oxo- l-norleucine. The protective effect of UDP-N-acetylglucosamine in vitro appears to explain the protective effect of glucosamine in vivo. The implications of these findings are discussed with respect to the nature of the interaction between the enzyme, its two substrates, its feedback inhibitor (UDP-N-acetylglucosamine) and the inactivator, 6-diazo-5-oxo- l-norleucine. This system provides a means of studying the synthesis of a specific constitutive enzyme under controlled conditions in the liver.

Early labeling with glucosamine- 14C of granular and agranular endoplasmic reticulum and free ribosomes from rat Liver

The initiation of carbohydrate prosthetic group attachment onto liver glycoprotein apopolypeptides occurs while the latter are still bound nascent to their sites of synthesis on endoplasmic reticulum-bound ribosomes. Free ribosomes or free polysomes appear to be inactive in glycoprotein initiation. Though initial incorporation of glucosamine- 14C is fastest into agranular reticulum glycoproteins, the granular reticulum soon attains a similar specific activity by 20–30 minutes after an intraperitoneal injection of glucosamine. The most active, early-labeled components of the agranular fraction are low-density membranes that differ from plasma membrane fragments and the Dallner subfractions of agranular reticulum.

Control of the Formation of Uridine Diphospho-N-acetyl-hexosamine and Glycoprotein Synthesis in Rat Liver

Abstract Rats fed a purified diet containing 1% orotic acid for 2 days accumulate large amounts of uridine diphospho-N-acetylhexosamine in the liver. This accumulation is not the result of a block in utilization of uridine diphospho-N-acetylhexosamine, but probably results from increased synthesis de novo. These rats appear to suffer from a defect in the feedback control of l-glutamine-d-fructose 6-phosphate amidotransferase by uridine diphospho-N-acetylglucosamine. The injection of glucosamine into control animals greatly reduces the synthesis de novo of glucosamine as measured by the incorporation of fructose into the glucosamine of uridine diphospho-N-acetylglucosamine. Duazomycin A, a glutamine analogue, completely prevents the synthesis de novo of glucosamine derivatives in the liver by inhibiting the amidotransferase, and reduces liver uridine diphospho-N-acetylhexosamine levels by 85% in 4 hours. Duazomycin A does not significantly reduce either the conversion of glucosamine to uridine diphospho-N-acetylhexosamine or the utilization of available uridine diphospho-N-acetylhexosamine for glycoprotein synthesis. Duazomycin A does inhibit glycoprotein synthesis indirectly, however, by reducing the level of uridine diphospho-N-acetylhexosamine in the liver. This reduction can be prevented by the infusion of glucosamine.

Insulin secretion in glucosamine-induced hyperglycemia in rats.

The hyperglycemia response produced by the injection of glucosamine in rats has been studied by comparing the effects of equal doses of glucosamine and glucose on blood glucose, circulating insulin, and pancreatic insulin content. The effect of glucosamine and glucose on insulin release from the islets has been studied in vitro by incubating slices of pancreas from normal rats and from rats injected with glucosamine. After glucosamine injection, the blood glucose rose and the circulating insulin decreased. In the glucose-injected group the hyperglycemia was lower and the circulating insulin higher. Insulin output from incubated pancreatic slices of normal rats rose when the glucose concentration in the medium was increased or when tolbutamide was added. A decrease below the base line occurred on the addition of glucosamine or when pancreas slices from glucosamine-injected rats were incubated. Insulin injection decreased the hyperglycemic effect of glucosamine whereas tolbutamide was ineffective. These results suggest that glucosamine exerts an inhibitory effect on insulin release from the pancreas.

BIOCHEMICAL STUDIES ON CARBOHYDRATES

Journal Article BIOCHEMICAL STUDIES ON CARBOHYDRATES: LIV. Hyperglycemia after Glucosamine Injection and the Mechanism of its Occurrence Get access MASATO YOSITAKE MASATO YOSITAKE Medico-Chemical Institute, Hokkaido Imperial UniversitySapporo Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 30, Issue 3, November 1939, Pages 439–449, https://doi.org/10.1093/oxfordjournals.jbchem.a125919 Published: 01 November 1939 Article history Received: 21 August 1939 Published: 01 November 1939