Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine transport was characterized in human umbilical artery smooth muscle cells isolated from non-diabetic and diabetic pregnant subjects. Transport of adenosine was mediated by a Na+-independent transport system inhibited by nanomolar concentrations of nitrobenzylthioinosine (NBMPR) in both cell types. Diabetes increased adenosine transport, an effect that was associated with a higher maximal velocity (Vmax) for NBMPR-sensitive (es) saturable nucleoside transport (18 +/- 2 vs. 61 +/- 3 pmol (microgram protein)-1 min-1, P < 0.05) and the maximal number of binding sites (Bmax) for specific [3H]NBMPR binding (74 +/- 4 vs. 156 +/- 10 pmol (microgram protein)-1, P < 0.05), with no significant changes in the Michaelis-Menten (Km) and dissociation (Kd) constants, respectively. Adenosine transport was unaltered by inhibition of nitric oxide (NO) synthase (with 100 microM NG-nitro-L-arginine methyl ester, L-NAME) or protein synthesis (with 1 microM cycloheximide), but was increased by inhibition of adenylyl cyclase activity (with 100 microM, SQ-22536) in non-diabetic cells. Diabetes-induced adenosine transport was blocked by L-NAME and associated with an increase in L-[3H]citrulline formation from L-[3H]arginine and intracellular cGMP, but with a decrease in intracellular cAMP compared with non-diabetic cells. Expression of inducible NO synthase (iNOS) was unaltered by diabetes. Dibutyryl cGMP (dbcGMP) increased, but dibutyryl cAMP (dbcAMP) decreased, adenosine transport in non-diabetic cells. dbcGMP or the NO donor S-nitrosoacetylpenicillamine (SNAP, 100 microM) did not alter the diabetes-elevated adenosine transport. However, activation of adenylyl cyclase with forskolin (1 microM), directly or after incubation of cells with dbcAMP, inhibited adenosine transport in both cell types. Our findings provide the first evidence that adenosine transport in human umbilical artery smooth muscle cells is mediated by the NBMPR-sensitive transport system es, and that its activity is upregulated by gestational diabetes.
 ...
PMID:Nitric oxide, cGMP and cAMP modulate nitrobenzylthioinosine-sensitive adenosine transport in human umbilical artery smooth muscle cells from subjects with gestational diabetes. 1091 79

The aim of this study was to examine if acute hyperglycemia (an oral glucose tolerance test) activates platelet function, endothelial cells or thrombin generation in diabetic patients and healthy controls. Eleven males with mild type II diabetes mellitus and 11 healthy male volunteers, matched for age and body mass index, were investigated before and after the glucose load. Soluble P-selectin, von Willebrand factor antigen and markers of thrombin generation in plasma were determined by immunoassays, and platelet P-selectin expression (unstimulated and agonist-stimulated) by flow cytometry in whole blood. Acute hyperglycemia elevated plasma soluble P-selectin from 32.5 to 50.9 ng/ml in the diabetic group (P = 0.05) but not in the controls (from 27.3 to 28.8 ng/ml; P = 0.6). Also, soluble P-selectin levels were higher in patients with diabetes than in healthy controls during hyperglycemia, but not in the fasting state. Adenosine diphosphate- and thrombin-induced platelet P-selectin expression was slightly, but significantly, decreased by the glucose load, whereas platelet P-selectin expression in unstimulated samples was not affected. Plasma levels of von Willebrand factor and thrombin generation were similar in patients and controls, and were not altered by hyperglycemia. In conclusion, we found that acute hyperglycemia elevates soluble P-selectin in plasma in males with mild type II diabetes mellitus. Our observation of unaltered plasma levels of the endothelial marker von Willebrand factor is in agreement with platelets being the main source of P-selectin released into plasma following hyperglycemia. Thus, platelets in individuals with type II diabetes may be more susceptible to hyperglycemia than platelets in non-diabetic individuals.
 ...
PMID:Acute hyperglycemia increases soluble P-selectin in male patients with mild diabetes mellitus. 1130 72

1. Adenosine transport was measured in human cultured umbilical artery smooth muscle cells, isolated from non-diabetic or gestational diabetic pregnancies, under basal conditions and after pretreatment in vitro with insulin. 2. Adenosine transport in non-diabetic smooth muscle cells was significantly increased by insulin (half-maximal stimulation at 0.33 +/- 0.02 nM, 8 h) and characterized by a higher maximal rate (V(max)) for nitrobenzylthioinosine (NBMPR)-sensitive (es) saturable nucleoside transport (17 +/- 5 vs. 52 +/- 12 pmol (microg protein)(-1) min(-1), control vs. insulin, respectively) and maximal binding sites (B(max)) for [(3)H]NBMPR (0.66 +/- 0.07 vs. 1.1 +/- 0.1 fmol (microg protein)(-1), control vs. insulin, respectively), with no significant changes in Michaelis-Menten (K(m)) and dissociation (K(d)) constants. 3. In contrast, in smooth muscle cells from diabetic pregnancies, where the values of V(max) for adenosine transport (59 +/- 4 pmol (microg protein)(-1) min(-1)) and B(max) for [(3)H]NBMPR binding (1.62 +/- 0.16 fmol (microg protein)(-1)) were significantly elevated by comparison with non-diabetic cells, insulin treatment (1 nM, 8 h) reduced the V(max) for adenosine transport and B(max) for [(3)H]NBMPR binding to levels detected in non-diabetic cells. 4. In non-diabetic cells, the stimulatory effect of insulin on adenosine transport was mimicked by dibutyryl cGMP (100 nM) and reduced by inhibitors of phosphatidylinositol 3-kinase (10 nM wortmannin), nitric oxide synthase (100 microM N (G)-nitro-L-arginine methyl ester, L-NAME) or protein synthesis (1 microM cycloheximide), whereas inhibition of adenylyl cyclase (100 microM SQ-22536) had no effect. 5. Wortmannin or SQ-22536, but not L-NAME or cycloheximide, attenuated the inhibitory action of insulin on the diabetes-induced stimulation of adenosine transport. 6. Protein levels of inducible NO synthase (iNOS) were similar in non-diabetic and diabetic cells, but were increased by insulin (1 nM, 8 h) only in non-diabetic smooth muscle cells. 7. Our results suggest that adenosine transport via the es nucleoside transporter is modulated differentially by insulin in either cell type. Insulin increased adenosine transport in non-diabetic cells via NO and cGMP, but inhibited the diabetes-elevated adenosine transport via activation of adenylyl cyclase, suggesting that the biological actions of adenosine may be altered under conditions of sustained hyperglycaemia in uncontrolled diabetes.
 ...
PMID:Modulation of adenosine transport by insulin in human umbilical artery smooth muscle cells from normal or gestational diabetic pregnancies. 1143 5

1. The aim of the present study was to investigate the inhibitory effects of adenosine on the contractile force and chronotropic action of isolated right atrial preparations from streptozotocin (STZ)-diabetic rats. 2. The rats were anaesthetized with diethyl ether and STZ (65 mg kg(-1)) was injected intravenously via the tail vein. 3. Adenosine produced concentration-dependent decreases in the force of contraction and a negative chronotropic action of atria both in control and diabetic groups. The inhibition responses to adenosine were significantly higher in diabetic rat atria than control. 4. Dypiridamole incubation caused a significant potentiation of the inhibitory effect of adenosine on contractile force and chronotropic action of atria in the control group, but not in the diabetic group. In the presence of dipyridamole, the inhibitory effects of adenosine on measured parameters in diabetic rats were not significantly different from those in control rats. 5. These results suggested that atria from 6 weeks STZ-diabetic rats exhibited a supersensitivity to the negative inotropic and chronotropic effects of adenosine compared with atria from control rats because of an impairment in adenosine uptake mechanism. Altered sensitivity to effects of adenosine might reflect relatively early changes in the course of diabetes.
 ...
PMID:The effects of adenosine on isolated right atrial preparations from streptozotocin-diabetic rats. 1195 74

Glomerular mesangial cells play a major role in glomerular hemodynamics, considered also as antigen-presenting cells participating in immune response. Mesangial dysfunction and proliferation are typical lesions of diabetic glomerulopathy. Adenosine, a local hormone, produced by mesangial cells is a metabolic regulator of renal blood flow, capable of decreasing glomerular filtration rate (GFR), exerting immunosuppressive, antiproliferative and anti-inflammatory properties. Since it was well established that antioxidants confer protection against increased oxidative stress that occurs in diabetes, the effect of captopril, reduced glutathione and melatonin on adenosine metabolism was investigated. Glomerular mesangial cells obtained from collagenase treated glomeruli, isolated from renal cortex of Sprague-Dowley rats, were grown under high glucose conditions (30 mmol/L) as a model of diabetic microenvironment. The activity of adenosine metabolizing enzymes: 5'-nucleotidease (5'-NU) responsible for its production and adenosine deaminase (ADA) responsible for its degradation were investigated. Hyperglycemic conditions led to decreased adenosine production via 5'-NU and decreased removal via ADA. Captopril, given in therapeutic concentration induced enzyme activities in normoglycemic conditions and restored hyperglycemia-induced decrease. In order to investigate if the presence of SH groups may be responsible for this improvement, the cells were exposed to reduced glutathione, and it exerted almost equal effect, given in physiological and higher concentrations. Melatonin increased 5'-NU activity only in physiological glucose conditions. Presented results confirm potential renoprotective effect of SH-group containing antioxidant supplementation during diabetes in restoring adenosine metabolism.
 ...
PMID:Antioxidants modulate adenosine metabolism in rat mesangial cells cultured under high glucose conditions. 1247 93

Advanced glycation end products (AGEs) are thought to be responsible for some complications of diabetes mellitus (DM), including microangiopathy. Plasma serotonin is increased in diabetes mellitus patients, and this increase is related, at least in part, to platelet hyperfunction. In order to clarify the relationship between advanced glycation end products, serotonin, and thrombotic complications in diabetes mellitus patients, we examined the effect of advanced glycation end products on serotonin-induced platelet aggregation. In diabetic patients, although serotonin-induced platelet aggregation was enhanced with an increase in serum-advanced glycation end products, there was no correlation between platelet aggregation and either hemoglobin A1c or fasting blood sugar. To examine the direct effect of advanced glycation end products on platelet aggregation, we prepared advanced glycation end products by in vitro incubation of human albumin with glucose (250 mM) at 37 degrees C for 8 weeks. Serotonin-induced platelet aggregation was dose-dependently increased by advanced glycation end products. Adenosine diphosphate-induced platelet aggregation also was increased by advanced glycation end products, but this increment was diminished by addition of sarpogrelate, a selective serotonin receptor antagonist. These results suggest that advanced glycation end products enhance platelet aggregation through the serotonin receptor, and perhaps influencing the development of thrombotic complications in diabetic patients.
 ...
PMID:Enhancing effect of advanced glycation end products on serotonin-induced platelet aggregation in patients with diabetes mellitus. 1256 18

Glomerular filtration rate (GFR) in response to adenosine precursor, NAD, and glomeruli contractility in response to adenosine were evaluated in streptozotocin-induced diabetic rats with severe (blood glucose 27.8 +/- 1.2 mmol/L) and moderate hyperglycaemia (18.2 +/- 0.9 mmol/L) compared with nondiabetic (ND)-rats. In anaesthetised rats, basal GFR was greater in moderately diabetic rats compared with severely diabetic rats (p < 0.05) and ND-rats (p < 0.02). Intravenous infusion of 5 nmol x min(-1) x kg(-1) NAD reduced GFR and renal plasma flow (RPF) in diabetic rats but had no effect on these parameters in ND-rats. Moreover, NAD-induced reduction of GFR and RPF was greater in rats with severe diabetes (41% and 30%, respectively) than in with moderate diabetes (25% and 26%, respectively). Theophylline (0.2 micromol x min(-1) x kg(-1) ) abolished renal response to NAD. Isolated glomeruli contraction in response to adenosine, assessed by glomerular 3H-inulin space reduction, was lowered in moderately diabetic-group and enhanced in severely diabetic-group. compared with ND-group (p < 0.05). Adenosine A1-receptor antagonist DPCPX inhibited adenosine-induced glomeruli contraction. This differential response of diabetic renal glomeruli to adenosine suggests that impaired glomerular contractility in response to adenosine could be responsible for hyperfiltration in moderate diabets, whereas, the increased adenosine-dependent contractility of glomeruli in severe diabetes may increase the risk of acute renal failure in this condition.
 ...
PMID:Responsiveness of renal glomeruli to adenosine in streptozotocin-induced diabetic rats dependent on hyperglycaemia level. 1267 23

A newly formulated solution consisting of lactobionate with or without histidine was tested in the preservation of the rat pancreas. Adult male Lewis rats weighing 120-250 g were used as donors and recipients. Fifty-four rat pancreas transplants were performed to investigate the effectiveness of this test solution and to compare it with the standard University of Wisconsin (UW) solution. The final osmolarity of the new test solution was 290-320 mosmol/l. This solution had a higher sodium content and lower potassium content (Na: 110 mEq/l, K: 50 mEq/l). Adenosine, insulin, hydroxyethyl starch and dexamethasone, which are components of the UW solution, were not present in this test solution. Histidine was used as a buffer. Rat pancreases were stored at 4 degrees C in either standard UW solution, or high-Na+-histidine solution, or high-Na+-lactobionate solution for 48 h and 72 h prior to heterotopic transplantation into rats with streptozotocin-induced diabetes mellitus. Functional success rates for rats receiving pancreases that had been preserved in high-Na+-histidine and in high-Na+-lactobionate solutions at 4 degrees C were 100% (5/5) and 100% (7/7) after 48 h preservation, and 50% (4/8) and 14% (1/7) after 72 h preservation, respectively. By contrast, standard UW solution gave only a 44% (4/9) success rate after 48 h preservation and a 0% (0/8) success rate after 72 h preservation. These results demonstrated that the high-Na+-histidine solution was superior to standard UW solution for rat pancreas preservation. This was probably due to the buffer, histidine, which prevented the acidosis of ischemic tissue during the period of preservation.
 ...
PMID:Prolonged rat pancreas preservation using a solution with the combination of histidine and lactobionate. 1462 16

Experiments were designed to determine whether experimental diabetes alters inotropic and chronotropic effects of adrenergic, adenosinergic, and cholinergic agonists and whether the observed changes are prevented by sodium selenate therapy. Thirty-two rats were divided into four groups of eight subjects each. Diabetes induced by streptozotocin caused significant decreases in isoproterenol-invoked contraction of the left atria with preservation of the right atrial chronotropic responses. The diminished response of the left atrial muscle to isoproterenol did not respond to treatment with sodium selenate. The left atria adenosine-induced direct- and indirect inotropic responses were diminished in the diabetic rats. After treatment with sodium selenate the direct response was completely normalized, but the indirect response was only partially corrected. Adenosine-induced negative chronotropic effects are accompanied by changed responses in diabetic right atria that are corrected after treatment. The carbachol-induced inotropic and chronotropic responses were not altered in tests of the acetylcholine system. We conclude that in diabetic rats, sodium selenate treatment reverses the deficits of adenosine-induced negative inotropic responses of left and right atria, but not those of isoproterenol-induced positive inotropic responses.
 ...
PMID:Effects of sodium selenate treatment on altered responses of left and right atria from streptozotocin-induced diabetic rats. 1517 52

Gestational diabetes is associated with increased L-arginine transport and nitric oxide (NO) synthesis, and reduced adenosine transport in human umbilical vein endothelial cells (HUVEC). Adenosine increases endothelial L-arginine/NO pathway via A(2) purinoceptors in HUVEC from normal pregnancies. It is unknown whether the effect of gestational diabetes is associated with activation of these purinoceptors or altered expression of human cationic amino acid transporter 1 (hCAT-1) or human equilibrative nucleoside transporter 1 (hENT1), or endothelial NO synthase (eNOS) in HUVEC. Cells were isolated from normal or gestational diabetic pregnancies and cultured up to passage 2. Gestational diabetes increased hCAT-1 mRNA expression (2.4-fold) and activity, eNOS mRNA (2.3-fold), protein level (2.1-fold), and phosphorylation (3.8-fold), but reduced hENT1 mRNA expression (32%) and activity. Gestational diabetes increased extracellular adenosine (2.7 microM), and intracellular L-arginine (1.9 mM) and L-citrulline (0.7 mM) levels compared with normal cells (0.05 microM, 0.89 mM, 0.35 mM, respectively). Incubation of HUVEC from normal pregnancies with 1 microM nitrobenzylthioinosine (NBMPR) mimicked the effect of gestational diabetes, but NBMPR was ineffective in diabetic cells. Gestational diabetes and NBMPR effects involved eNOS, PKC and p42/44(mapk) activation, and were blocked by the A(2a) purinoceptor antagonist ZM-241385. Thus, gestational diabetes increases the L-arginine/NO pathway involving activation of mitogen-activated protein (MAP) kinases, protein kinase C (PKC) and NO cell signalling cascades following activation of A(2a) purinoceptors by extracellular adenosine. A functional relationship is proposed between adenosine transport and modulation of L-arginine transport and NO synthesis in HUVEC, which could be determinant in regulating vascular reactivity in diabetes mellitus.
 ...
PMID:Role of adenosine transport in gestational diabetes-induced L-arginine transport and nitric oxide synthesis in human umbilical vein endothelium. 1527 35


<< Previous 1 2 3 4 5 6 7 8 9 Next >>