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

We have investigated whether nitric oxide (NO) generation is increased in diabetes and whether specific NO synthase (NOS) isoforms are up-regulated in 4-week diabetic male Wistar rats. Glomerular filtration rate (GFR), kidney weight, and urinary nitrate (NOx) generation were measured in the following groups (n = 6): normal control animals, diabetic animals, diabetic animals given L -NIL (a selective iNOS inhibitor)(D + L -NIL), diabetic animals given L -NAME (a nonselective NOS inhibitor)(D + L -NAME), and control animals given L -NAME (C + L -NAME). Diabetes increased GFR (0.78 +/- 0.05 mL/min/100 g body wt vs 1.49 +/- 0.07 mL/min/100 g body wt, P <.01). L -NIL did not affect hyperfiltration, while L -NAME decreased GFR to values that were lower than those in normal control animals, a response identical to that in non-diabetic control rats. L -NIL did not affect urinary NOx values, but L -NAME completely abolished the increase in urinary nitrates. Kidney weight was not affected by L -NIL, but L -NAME significantly attenuated kidney growth. Inducible NOS (iNOS) and endothelial NOS (eNOS) mRNA levels measured by reverse transcription-polymerase chain reaction in diabetic rats were not changed as compared with levels in controls. Cyclic guanosine monophosphate responses to carbachol (an index of eNOS activity) in glomeruli from diabetic rats were significantly reduced as compared with those in controls, and guanylate cyclase responses to sodium nitroprusside were significantly decreased. Therefore, renal NO generation, at least via eNOS and iNOS, is not the primary cause of glomerular hyperfiltration in diabetes.
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PMID:An analysis of renal nitric oxide contribution to hyperfiltration in diabetic rats. 1117 67

The cytokine-induced overproduction of nitric oxide by immunocompetent cells with subsequent development of oxidative stress is suggested to be one of important pathophysiological mechanisms of the pancreatic beta cells damage in streptozotocin-induced experimental diabetes. The aim of our study was to compare the influence of two nitric oxide inhibiting compounds: methylene blue and L-NAME (N-omega-nitro-L-arginine-methyl ester) on the streptozotocin diabetes development and the oxidative stress parameters in male rats. Blood glucose, glycated haemoglobin, serum malondialdehyde concentration and erythrocyte superoxide dismutase activity were measured in control, diabetic (streptozotocin 70 mg/kg i.p.), methylene blue (50 mg/kg in the food), and diabetic group treated simultaneously with methylene blue (10 animals in each group). In the second experiment the L-NAME was used instead of methylene blue. It was found that both methylene blue and L-NAME partially suppressed the development of diabetes, but did not unambiguously influence the oxidative stress parameters. We conclude, that both methylene blue and L-NAME partially suppress the development of streptozotocin-induced diabetes in rats. The precise mechanism of this effect is not clear. We failed to demonstrate clear effect of methylene blue and/or L-NAME on oxidative stress development in diabetic rats.
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PMID:The influence of methylene blue and L-NAME on the development of streptozotocin-induced diabetes in rats. 1122 68

Microvascular reactivity of cannulated and pressurised rat cremaster arterioles was studied during the progress of diabetes using mechanical (intraluminal pressure) and chemical (acetylcholine, sodium nitroprusside) stimulation. Microvessels were studied in controls and at 2, 4 and 8 weeks following induction of diabetes by streptozotocin. Mechanical responses were stable at the test pressure (70 mmHg) used for pharmacological investigations during the period of diabetes. Acetylcholine application could induce maximal dilatation in control vessels and in vessels exposed to 8 weeks of diabetes. However, acetylcholine administration failed to generate maximal dilatation at 2 and 4 weeks of diabetes. During the period of diabetes, loss of nitric oxide (NO) pathway effectiveness was revealed by diminished response to sodium nitroprusside and by reduced capacity of Nomega-nitro-L-arginine methyl ester (L-NAME) to decrease resting diameter and acetylcholine-evoked dilatation. L-NAME and indomethacin application revealed a significant non-NO, non-prostaglandin contribution to the acetylcholine response at 4 and 8 weeks of diabetes. Recovery of responsiveness to acetylcholine and stabilisation of resting vessel diameter during diabetes may, in part, be due to increasing effectiveness of non-NO, non-prostaglandin pathways.
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PMID:Recovery of microvascular responses during streptozotocin-induced diabetes. 1123 Sep 96

Insulin, contraction, and the nitric oxide (NO) donor, sodium nitroprusside (SNP), all increase glucose transport in skeletal muscle. Some reports suggest that NO is a critical mediator of insulin- and/or contraction-stimulated transport. To determine if the mechanism leading to NO-stimulated glucose uptake is similar to the insulin- or contraction-dependent signaling pathways, isolated soleus and extensor digitorum longus (EDL) muscles from rats were treated with various combinations of SNP (maximum 10 mmol/l), insulin (maximum 50 mU/ml), electrical stimulation to produce contractions (maximum 10 min), wortmannin (100 nmol/l), and/or the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) (0.1 mmol/l). The combinations of SNP plus insulin and SNP plus contraction both had fully additive effects on 2-deoxyglucose uptake. Wortmannin completely inhibited insulin-stimulated glucose transport and only slightly inhibited SNP-stimulated 2-deoxyglucose uptake, whereas L-NMMA did not inhibit contraction-stimulated 2-deoxyglucose uptake. SNP significantly increased the activity of the alpha1 catalytic subunit of 5'AMP-activated protein kinase (AMPK), a signaling molecule that has been implicated in mediating glucose transport in fuel-depleted cells. Addition of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mg/ml) to the drinking water of rats for 2 days failed to affect the increase in muscle 2-deoxyglucose uptake in response to treadmill exercise. These data suggest that NO stimulates glucose uptake through a mechanism that is distinct from both the insulin and contraction signaling pathways.
Diabetes 2001 Feb
PMID:Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle. 1127 32

Diabetes is associated with impaired cardiovascular responses that are especially prominent in females. Since nitric oxide (NO)-mediated effects on cardiovascular dynamics are altered in diabetes, we evaluated the effect of L-NAME, a nitric oxide synthase (NOS) antagonist, on mean arterial pressure (MAP), heart rate (HR), and selective vascular flows in both male and female normal and diabetic rats as an index of NO activity. Rats were made diabetic using streptozotocin and maintained for 5-6 weeks. Following anesthesia with urethane/alpha-chloralose, the femoral artery and vein were cannulated for recording and sampling, and flow probes were placed on the iliac, renal, and superior mesenteric arteries. A bolus infusion of L-NAME (10mg/ kg) resulted in a rapid +52% and +68% increase in MAP in normal female and male rats, respectively. However, diabetic females' and males' responses were significantly lower (44% and 45%, respectively) when compared with their normal counterparts. The decreased HR in response to the peak pressor effect of L-NAME was more prominent in normal females compared with normal males (-14% vs 2%). The results in diabetic females and males were equivalent (-6% vs -9%, respectively). L-NAME decreased the conductance (flow/MAP) an average of 65% in all three vascular beds in normal female rats. In diabetic females, the iliac and superior mesenteric responses to L-NAME were less, and the renal conductance was contrastingly increased 23%. The response to L-NAME was comparable (-62%) in the renal and superior mesenteric and less (-40%) in the iliacs of normal versus diabetic males. We concluded that diabetes is associated with a decreased pressor response to NOS inhibition. And the impaired constriction response of the renal vessels noted in female diabetic rats may provide a basis for the increased renal pathology observed in diabetic humans.
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PMID:The effect of diabetes and sex on nitric oxide-mediated cardiovascular dynamics. 1136 36

1. The pylorus plays an important role in the regulation of gastric emptying. In addition to the autonomic neuropathy associated with long-standing diabetes, acute hyperglycaemia per se has effects on gastric emptying. In this study, the role of the central nervous system in modulating the effects of hyperglycaemia on gastric distension-induced pyloric relaxation was investigated. 2. Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg(-1)) and N (G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1)), a nitric oxide synthase (NOS) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg(-1)) had an effect. 3. An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which increased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhibited gastric distension-induced pyloric relaxation. 4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 micromol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations. 5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide Y (NPY) concentrations. 6. Intracerebroventricular (I.C.V.) administration of NPY (0.03--3 nmol) and a Y1 receptor agonist, [leu(31), pro(34)] NPY (0.03--3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependent manner. 7. I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 microl) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation. 8. Taken together, these findings suggest that gastric distension-induced pyloric relaxation is mediated via a vago-vagal reflex and NO release. Acute hyperglycaemia stimulates hypothalamic NPY release, which, acting through the Y1 receptor, inhibits gastric distension-induced pyloric relaxation in rats exposed to acute elevations in blood glucose concentrations.
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PMID:Gastric distension-induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat. 1141 Jun 36

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.
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PMID:Modulation of adenosine transport by insulin in human umbilical artery smooth muscle cells from normal or gestational diabetic pregnancies. 1143 5

The renal excretory responses to volume expansion (VE), by 10 % body wt, were determined in groups of anaesthetised streptozotocin-induced diabetic rats with one denervated and one innervated kidney in the presence and absence of nitric oxide synthase (NOS) inhibitors. VE in diabetic rats increased (P < 0.001) cumulative urine sodium excretion (CuU(Na)V) to 104 +/- 9 and 69 +/- 6 micromol min(-1) (g kidney wt)(-1) in the denervated and in the innervated kidneys, respectively, which were both less (P < 0.001) than in the non-diabetic rats, at 225 +/- 14 and 148 +/- 14 micromol min(-1) (g kidney wt)(-1), respectively, in the denervated and the innervated kidney. The non-selective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME) given to the diabetic rats with intact renal innervation enhanced CuU(Na)V after VE by 43 % (P < 0.001), while the combination of L-NAME and renal denervation restored CuU(Na)V to a value comparable to that of non-diabetic rats. In diabetic rats treated with either a relatively selective inhibitor for the neuronal isoform of NOS, 7-nitroindazole, or a relatively selective inhibitor for the inducible isoform of NOS, aminoguanidine, CuU(Na)V after VE was similar to the untreated diabetic rats irrespective of whether or not the renal nerves were present. This investigation demonstrated that NO production contributed, at least partly, to the depressed ability to excrete a saline load in diabetes mellitus. The endothelial isoform of NOS was most probably responsible for generating NO which caused the blunted excretory responses. The ability of NO to attenuate the excretory responses to volume expansion was an action independent of the renal innervation status. Experimental Physiology (2001) 86.4, 481-488.
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PMID:Contribution of endothelial nitric oxide synthase in the blunted renal responses to volume expansion in diabetic rats. 1144 27

Electrical field stimulation (4 Hz, 0.2 ms pulse duration, at a supramaximal voltage of 70 V, for 1 s) of isolated rat tail artery segments produced contraction which was lower in female than in male rats, and was reduced by streptozotocin-induced diabetes in both genders. This contraction was potentiated by vasopressin (10(-12)-10(-10) M) more in normoglycemic male than in normoglycemic female rats, and this effect of vasopressin was increased by the cyclooxigenase inhibitor meclofenamate (10(-5) M) in female control rats, but not in diabetic female, or control and diabetic male rats, and it was not modified by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). Endothelin-1 (10(-10)-3 x 10(-9) M) also potentiated the contraction to electrical stimulation. This potentiation was similar in all experimental groups, and it was not modified by meclofenamate or L-NAME. These results suggest that the potentiating effect of vasopressin, but not that of endothelin-1, on the sympathetic vasoconstriction, is lower in females than in males, probably by an increased release of vasodilating prostanoids, and this release may be reduced by diabetes in females.
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PMID:Diabetes abolishes the gender difference in vasopressin-mediated potentiation of sympathetic vasoconstriction. 1156 55

Cytokines and nitric oxide (NO) have been implicated in bone loss caused by estrogen deficiency. Here we evaluated the effect of nitric oxide synthase (NOS) inhibitors on the bone particle resorbing activity and TNF-alpha release of cultured peripheral blood monocytes (PBM) obtained from 10 premenopausal (PreM) and 10 postmenopausal (PostM) women. Gonadal status (menopause < 3 yr) was assessed by FSH and estradiol. Bone alkaline phosphatase and N-Telopeptide were significantly increased in PostM. Significant differences between PreM and PostM women were observed in bone mineral density of lumbar spine. The bone particle resorbing activity of PBM cultured in the presence of L-arginine-methyl ester (NAME) or aminoguanidine, NOS inhibitors, was determined by (45)Ca release from rat bone labeled particles. TNF-alpha release was assayed in supernatants by ELISA. (45)Ca release was higher in PostM (p < 0.01) and was enhanced by NAME (p < 0.02). Furthermore, TNF-alpha release from PBM was significantly higher in PostM (p < 0.01). Aminoguanidine significantly increased TNF-alpha release in PreM. Based on these findings and on the evidence that estrogen stimulates NOS, we suggest that estrogen withdrawal may reduce the inhibitory effect of NO on TNF-alpha release. Thus, this increased production of TNF-alpha could contribute to the increased postmenopausal bone turnover.
Exp Clin Endocrinol Diabetes 2001
PMID:Estrogenic status influences nitric oxide-regulated TNF-alpha release from human peripheral blood monocytes. 1157 73


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