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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucosamine has a major influence on the impairment of some metabolic mechanisms in the human body. As shown in vitro experiments, it takes part in inducing mechanisms of insulin resistance. Therefore, the purpose of our study was to evaluate glucosamine levels in the serum of patients who suffered myocardial infarction (MI) and who either had or didn't have diagnosed type II diabetes in relation to healthy people. The levels of glucosamine, immunoreactive insulin, C-peptide, glucose and lipid indexes were measured in venous blood in investigated patients. In patients with MI without diabetes the highest concentrations of glucosamine, insulin and C-peptide were noted as compared to the results obtained from other groups of patients. In patients with diabetes, on the other hand, the highest glucose levels were noted as compared to the results of other patients. There were no statistically differences of lipid indexes between two groups of patients following MI. A negative correlation between glucosamine levels and glucose concentrations in patients without diabetes may suggest that glucose does not directly determine glucosamine levels. The returning of insulin levels to normal in patients with hyperinsulinemia (antidiabetic drugs) may play a role in the lowering of glucosamine induced peripheral insulin resistance.
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PMID:Glucosamine levels in people with ischaemic heart disease with and without type II diabetes. 1041 May 75

To explore potential cellular mechanisms by which activation of the hexosamine pathway induces insulin resistance, we have evaluated insulin signaling in conscious fasted rats infused for 2-6 h with saline, insulin (18 mU x kg(-1) x min(-1)), or insulin and glucosamine (30 micromol x kg(-1) x min(-1)) under euglycemic conditions. Glucosamine infusion increased muscle UDP-N-acetylglucosamine concentrations 3.9- and 4.3-fold over saline- or insulin-infused animals, respectively (P < 0.001). Glucosamine induced significant insulin resistance to glucose uptake both at the level of the whole body and in rectus abdominis muscle, and it blunted the insulin-induced increase in muscle glycogen content. At a cellular level, these metabolic effects were paralleled by inhibition of postreceptor insulin signaling critical for glucose transport and glycogen storage, including a 45% reduction in insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation (P = 0.02), a 44% decrease in IRS-1 association with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase (P = 0.03), a 34% reduction in IRS-1-associated PI 3-kinase activity (P = 0.03), and a 51% reduction in insulin-stimulated glycogen synthase activity (P = 0.03). These alterations in postreceptor insulin signaling were time-dependent and paralleled closely the progressive inhibition of systemic glucose disposal from 2 to 6 h of glucosamine infusion. We also demonstrated that glucosamine infusion results in O-linked N-acetylglucosamine modification of IRS-1 and IRS-2. These data indicate that activation of the hexosamine pathway may directly modulate early postreceptor insulin signal transduction, perhaps via posttranslation modification of IRS proteins, and thus contribute to the insulin resistance induced by chronic hyperglycemia.
Diabetes 1999 Aug
PMID:Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. 1042 74

Hybrid receptors composed of an insulin alphabeta-hemireceptor and a type 1 IGF alphabeta-hemireceptor are formed in tissues expressing both molecules. We recently reported an increased hybrid receptor expression in skeletal muscle of type 2 diabetic patients that is inversely correlated with in vivo insulin sensitivity. It is unclear whether these changes were due to primary abnormalities or to secondary derangements acting in vivo, such as hyperglycemia. To address this, we determined abundance of hybrids in skeletal muscle from three groups of rats: controls, diabetic (90% pancreatectomy), and diabetic treated with phlorizin to normalize plasma glucose levels. We found that the abundance of hybrid receptors was higher in diabetic rats compared with control and phlorizin-treated diabetic rats (percentage of 125I-insulin bound versus total added radioactivity [B/T] = 1.8+/-0.11, 0.4+/-0.01, and 0.32+/-0.04, respectively; P < 0.0001). Fasting plasma glucose levels were positively correlated with hybrids abundance (r = 0.77, P < 0.002). Hybrid receptor protein content, assessed by immunoblotting, was 2.4-fold higher in diabetic rats as compared with control and phlorizin-treated diabetic rats. Because it has been shown that some of the regulatory effects of glucose may be mediated by the glucosamine pathway, we subsequently determined the effect of an in vivo glucosamine infusion on hybrid receptor formation. We found that abundance of hybrids was significantly higher in muscle from glucosamine-treated rats compared with control rats (B/T = 0.17+/-0.02 and 0.11+/-0.01, respectively; P < 0.009). Quantitation of hybrid content by immunoblotting revealed that their abundance was 1.9-fold higher in glucosamine-treated rats. The results demonstrate that 1) elevated glucose levels in diabetic rats are associated with increased expression of hybrid receptors in muscle, 2) correction of hyperglycemia with phlorizin completely reverses increased expression of hybrids, and 3) glucosamine infused into control rats mimics the effects of hyperglycemia on hybrid receptor formation. Thus, the results support the hypothesis that glucose acting, at least in part, through the glucosamine pathway may play an important role in regulating hybrid receptor assembly in vivo.
Diabetes 1999 Dec
PMID:Evidence for glucose/hexosamine in vivo regulation of insulin/IGF-I hybrid receptor assembly. 1058 Apr 14

Streptozotocin has been widely used to create animal models of diabetes. Structurally, streptozotocin resembles N-acetylglucosamine, with a nitrosourea group corresponding to the acetate present in N-acetylglucosamine. Streptozotocin has recently been shown to inhibit O-GlcNAc-selective N-acetyl-beta-d-glucosaminidase, which removes O-linked N-acetylglucosamine from proteins. Compared to other cells, beta-cells express much more of the enzyme O-GlcNAc transferase, which catalyzes addition of O-linked N-acetylglucosamine to proteins. This suggests why beta-cells might be particularly sensitive to streptozotocin. In this report, we demonstrate that both streptozotocin and glucose stimulate O-glycosylation of a 135 kD beta-cell protein. Only the effect of glucose, however, was blocked by inhibition of fructose-6-phosphate amidotransferase, suggesting that glucose acts through the glucosamine pathway to provide UDP-N-acetylglucosamine for p135 O-glycosylation. The fact that both glucose and streptozotocin stimulate p135 O-glycosylation provides a possible mechanism by which hyperglycemia may cause streptozotocin-like effects in beta-cells and thus contribute to the development of type 2 diabetes.
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PMID:Glucose and streptozotocin stimulate p135 O-glycosylation in pancreatic islets. 1062 69

This review article begins by discussing the molecular basis of the blood anticoagulant effect of heparin and some species of heparan sulphate (HS). A highly specific pentasaccharide sequence, containing a glucosamine 3-O-sulphate group, is a key structural element for this action. The biosynthesis of heparin and HS is outlined. Different types of HS proteoglycans exist. Analysis of HS preparations from different mammalian organs has indicated that the structural variability of the polysaccharide is due to regulated polymer modification. In addition to antithrombin, HS chains bind a very large number of other proteins in vivo. Such binding often appears to depend on the presence of specific sequences of different monosaccharide building-blocks and has diverse implications. Many physiological and pathological processes in the mammalian body appear to be influenced or regulated by HS proteoglycans. For example, the proper assembly of HS chains is believed to play an important role in normal embryonic and mammalian development. Diseases such as diabetes, amyloidosis and Alzheimer's may be associated with changes in HS structure. Finally, the possibilities and strategies for developing drugs based on HS chemistry are discussed.
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PMID:What else can 'Heparin' do? 1062 3

We used wild-type (WT) mice and mice engineered to express either apoB-100 only (B100 mice) or apoB-48 only (B48 mice) to examine the effects of streptozotocin-induced diabetes (DM) on apoB-100- and apoB-48-containing lipoproteins. Plasma lipids increased with DM in WT mice, and fat tolerance was markedly impaired. Lipoprotein profiles showed increased levels and cholesterol enrichment of VLDL in diabetic B48 mice but not in B100 mice. C apolipoproteins, in particular apoC-I in VLDL, were increased. To investigate the basis of the increase in apoB-48 lipoproteins in streptozotocin-treated animals, we characterized several parameters of lipoprotein metabolism. Triglyceride and apoB production rates were normal, as were plasma lipase activity, VLDL glycosaminoglycan binding, and VLDL lipolysis. However, beta-VLDL clearance decreased due to decreased trapping by the liver. Whereas LRP activity was normal, livers from treated mice incorporated significantly less sulfate into heparan sulfate proteoglycans (HSPG) than did controls. Hepatoma (HepG2) cells and endothelial cells cultured in high glucose also showed decreased sulfate and glucosamine incorporation into HSPG. Western blots of livers from diabetic mice showed a decrease in the HSPG core protein, perlecan. Delayed clearance of postprandial apoB-48-containing lipoproteins in DM appears to be due to decreased hepatic perlecan HSPG.
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PMID:Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice. 1086 96

Increased flux through the hexosamine biosynthetic pathway is associated with altered gene expression. To investigate the underlying mechanisms, we treated glomerular mesangial cells with glucosamine and studied the regulation of the plasminogen activator inhibitor (PAI)-1 gene. Incubating mesangial cells with 2 mmol/l glucosamine for 4 days resulted in a 3.1+/-0.4-fold increase in PAI-1 mRNA levels (P < 0.01) and a 33+/-9-fold increase in the activity of a transiently transfected PAI-1 promoter-luciferase reporter gene (P < 0.01). Cotransfection of an expression vector for a dominant-negative type II TGF-beta receptor with the PAI-1 promoter-reporter gene did not interfere with this effect of glucosamine. However, mutation of 2 putative Sp1 sites in the PAI-1 promoter, at -76 to -71 and -44 to -39, markedly reduced induction of PAI-1 luciferase activity by glucosamine, from 8.9+/-1.9-fold to 1.7+/-0.5-fold (P < 0.01). An electrophoretic mobility shift assay demonstrated that glucosamine increased Sp1 DNA binding by 31+/-11% (P < 0.05), implying that the effects of glucosamine were explained, in part, by changes in Sp1 DNA binding. High glucose (20 mmol/l) also activated the transiently transfected PAI-1 promoter (2.5+/-0.4-fold). This effect was diminished by mutation of both the PAI-1 promoter Sp1 sites (1.2+/-0.3-fold, P < 0.05). In addition, 6-diazo-5-oxo-L-norleucine, a glutamine:fructose-6-phosphate-amidotransferase inhibitor, blocked the induction by high glucose (4.7+/-0.8- to 0.9+/-0.1-fold, P < 0.01). These results indicate that stimulation of the PAI-1 promoter by both high glucose and glucosamine involves Sp1 and that the hexosamine pathway may be involved in the regulation of gene expression by high glucose in glomerular mesangial cells.
Diabetes 2000 May
PMID:Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells. 1090 98

To examine the effect of increased hexosamine flux in liver, the rate-limiting enzyme in hexosamine biosynthesis (glutamine:fructose-6-phosphate amidotransferase [GFA]) was overexpressed in transgenic mice using the PEPCK promoter. Liver from random-fed transgenic mice had 1.6-fold higher GFA activity compared with nontransgenic control littermates (276 +/- 24 pmol x mg(-1) x min(-1) in transgenic mice vs. 176 +/- 18 pmol x mg(-1) x min(-1) in controls, P < 0.05) and higher levels of the hexosamine end product UDP-N-acetyl glucosamine (288 +/- 11 pmol/g in transgenic mice vs. 233 +/- 10 pmol/g in controls, P < 0.001). Younger transgenic mice compared with control mice had lower fasting serum glucose (4.8 +/- 0.5 mmol/l in transgenic mice vs. 6.5 +/- 0.8 mmol/l in controls, P < 0.05) without higher insulin levels (48.0 +/- 7.8 pmol/l in transgenic mice vs. 56.4 +/- 5.4 pmol/l in controls, P = NS); insulin levels were significantly lower in transgenic males (P < 0.05). At 6 months of age, transgenic animals had normal insulin sensitivity by the hyperinsulinemic clamp technique. Hepatic glycogen content was higher in the transgenic mice (108.6 +/- 5.2 pmol/g in transgenic mice vs. 32.8 +/- 1.3 micromol/g in controls, P < 0.01), associated with an inappropriate activation of glycogen synthase. Serum levels of free fatty acids (FFAs) and triglycerides were also elevated (FFAs, 0.67 +/- 0.03 mmol/l in transgenic mice vs. 0.14 +/- 0.01 in controls; triglycerides, 1.34 +/- 0.15 mmol/l in transgenic mice vs. 0.38 +/- 0.01 in controls, P < 0.01). Older transgenic mice became heavier than control mice and exhibited relative glucose intolerance and insulin resistance. The glucose disposal rate at 8 months of age was 154 +/- 5 mg x kg(-1) x min(-1) in transgenic mice vs. 191 +/- 6 mg x kg(-1) x min(-1) in controls (P < 0.05). We conclude that hexosamines are mediators of glucose sensing for the regulation of hepatic glycogen and lipid metabolism. Increased hexosamine flux in the liver signals a shift toward fuel storage, resulting ultimately in obesity and insulin resistance.
Diabetes 2000 Dec
PMID:Overexpression of glutamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance. 1111 9

The present study was designed to clarify the effect of low molecular weight (LMW) chitosan (chitosan lactate, average MW: 20000) on the progression of slowly progressive non-insulin-dependent diabetes mellitus (NIDDM) induced by a single i.p. injection of low dose (100 mg/kg) streptozotocin (STZ) to 8-week-old male ICR mice. The non-fasting serum glucose levels of STZ-treated control mice continued to rise throughout the experimental period until 23 weeks after STZ treatment. The 0.2% or 0.8% chitosan (water solution), given as drinking water from prediabetic stage (2 weeks after STZ treatment), markedly prevented the time course-related rise of serum glucose levels of diabetic mice. In addition, the reduction of relative numbers of insulin-immunoreactive cells (beta-cells) in the islets of diabetic mice at 24 weeks after STZ treatment was markedly prevented by 0.2% or 0.8% chitosan administration. However, the progression of hyperglycemia in diabetic mice was not affected by 0.2% glucosamine, a monosaccharide of chitosan. The glucose levels of normal mice were not affected by 0.8% chitosan administration. When 0.2% chitosan administration was stopped at 20 weeks, these animals had still maintained significantly lower serum glucose levels, compared to control animals, even at 5 weeks after stopping the administration. These results indicate that LMW chitosan prevents the progression of low dose STZ-induced slowly progressive NIDDM.
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PMID:Low molecular weight chitosan prevents the progression of low dose streptozotocin-induced slowly progressive diabetes mellitus in mice. 1114 78

The infusion of glucosamine causes insulin resistance, presumably by entering the hexosamine biosynthetic pathway; it has been proposed that this pathway plays a role in hyperglycemia-induced insulin resistance. This study was undertaken to determine if glucosamine infusion could influence exercise-stimulated glucose uptake. Male SD rats were infused with glucosamine at 0.1 mg x kg(-1) x min(-1) (low-GlcN group), 6.5 mg x kg(-1) x min(-1) (high-GlcN group), or saline (control group) for 6.5 h and exercised on a treadmill for 30 min (17 m/min) at the end of the infusion period. Glucosamine infusion caused a modest increase in basal glycemia in both experimental groups, with no change in tracer-determined basal glucose turnover. During exercise, glucose turnover increased approximately 2.2-fold from 46 +/- 2 to 101 +/- 5 pmol x kg(-1) x min(-1) in the control group. Glucose turnover increased to a lesser extent in the glucosamine groups and was limited to 88% of control in the low-GlcN group (47 +/- 2 to 90 +/- 3 pmol x kg(-1) x min(-1); P < 0.01) and 72% of control in the high-GlcN group (43 +/- 1 to 73 +/- 3 pmol kg(-1) 1 min(-1); P < 0.01). Similarly, the metabolic clearance rate (MCR) in the control group increased 72% from 6.1 +/- 0.2 to 10.5 +/- 0.7 ml kg(-1) x min(-1) in response to exercise. However, the increase in MCR was only 83% of control in the low-GlcN group (5.2 +/- 0.5 to 8.7 +/- 0.5 ml x kg(-1) x min(-1); P < 0.01) and 59% of control in the high-GlcN group (4.5 +/- 0.2 to 6.2 +/- 0.3 ml x kg(-1) x min(-1); P < 0.01). Neither glucosamine infusion nor exercise significantly affected plasma insulin or free fatty acid (FFA) concentrations. In conclusion, the infusion of glucosamine, which is known to cause insulin resistance, also impaired exercise-induced glucose uptake. This inhibition was independent of hyperglycemia and FFA levels.
Diabetes 2001 Jan
PMID:Exercise-stimulated glucose turnover in the rat is impaired by glucosamine infusion. 1114 79


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