Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to examine the role of nitric oxide in the effects of hypoglycemia on the cerebral circulation. Hypoglycemia was induced with insulin and its effects on cerebral blood flow (measured with an electromagnetic flow transducer placed on the internal maxillary artery) were studied in awake goats under control conditions and after administration of the nitric oxide synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 47 mg/kg). Also, cerebrovascular reactivity to vasodilator stimuli was examined during insulin-induced severe hypoglycemia, before and after L-NAME treatment. In five animals under control conditions (glycemia = 90 +/- 7 mg/dl, cerebral blood flow = 64 +/- 4 ml/min, mean systemic arterial pressure = 102 +/- 4 mmHg, cerebrovascular resistance = 1.62 +/- 0.11 mmHg/ml per min and heart rate = 73 +/- 6 beats/min), insulin decreased glycemia: when hypoglycemia was moderate (glycemia = 46 +/- 2 mg/dl) or severe (glycemia = 26 +/- 1 mg/dl) cerebral blood flow increased by 25 +/- 4% and 47 +/- 6%, and cerebrovascular resistance decreased by 18 +/- 3% and 34 +/- 4%, respectively. Under basal conditions, L-NAME did not affect glycemia but reduced resting cerebral blood flow by 37 +/- 2%, increased mean arterial pressure by 33 +/- 2% and decreased heart rate by 28 +/- 3%; after L-NAME, both moderate and severe hypoglycemia did not alter significantly resting cerebral blood flow and cerebrovascular resistance. In five other goats, L-NAME, administered during severe hypoglycemia, abolished the increase in cerebral blood flow, and increased cerebrovascular resistance and mean arterial pressure over the control (normoglycemic) values. In these animals with severe hypoglycemia, acetylcholine (0.01-1 microg), isoproterenol (0.03-3 microg) and diazoxide (0.3-9 mg), injected into the internal maxillary artery, decreased cerebrovascular resistance in a dose-dependent manner, and this decrease was similar before and after L-NAME. Therefore, insulin-induced hypoglycemia may produce cerebral vasodilatation by releasing nitric oxide and may diminish the capacity of the cerebral vasculature to release nitric oxide in response to acetylcholine.
 ...
PMID:Role of nitric oxide in the effects of hypoglycemia on the cerebral circulation in awake goats. 925 52

In the rat, simple carbohydrate feeding induces insulin resistance, and insulin resistance is associated with impaired endothelium dependent vasodilation. To determine if increasing insulin sensitivity corrects this defect of endothelial function, we evaluated the effects of an insulin-sensitizing agent, pioglitazone, on arterial pressure and in vitro vascular reactivity in three groups of Sprague Dawley rats: 1) control; 2) 60% fructose diet for 4 weeks; 3) 60% fructose diet plus pioglitazone (20 mg/kg daily, by oral gavage). Direct mean arterial pressure did not differ in Groups 1 (120 mm Hg +/- 2) and 2 (121 +/- 2) and was lower (P < .05) in Group 3 (112 +/- 2). In vitro uptake of tritiated glucose by adipocytes in response to insulin was reduced (P < .05) by fructose and increased (P < .01) by pioglitazone. In strips of thoracic aorta, norepinephrine-induced vasoconstriction and nitroprusside induced vasodilation did not differ among groups. However, in response to graded dose of acetylcholine, vasodilation was reduced (P < .05) by fructose; this was normalized by pioglitazone. In all groups, N(G)-nitro-L-arginine methyl ester (L-NAME) completely blocked acetylcholine-induced vasodilation. Thus, pioglitazone increased insulin sensitivity, lowered blood pressure, and normalized acetylcholine-induced vasodilation in insulin resistant, fructose-fed rats. Increasing insulin sensitivity may lower arterial pressure by augmenting endothelium dependent vasodilation.
 ...
PMID:Increasing insulin sensitivity lowers blood pressure in the fructose-fed rat. 932 8

Significant changes in gastrointestinal function, decreased gastric secretion and motility in particular, are often observed in patients with chronic diabetes. The mechanisms leading to those remain unclear. In these studies we evaluated the gastric acid secretory response to insulin and pentagastrin in normal Wistar and streptozotocin diabetic rats. We also sought to determine the role of nitric oxide (NO) in this process. The animals were anesthetized with sodium pentobarbital. Warm saline was perfused through a polyethylene tube placed in the oesophagus and collected from the duodenum at 10 min intervals. Following a 50 min equilibration period, a bolus intra-jugular infusion of insulin (4.0 U/kg), 2-deoxyglucose (200 mg/kg) or pentagastrin 4.0 (ug/kg) was started and samples of the gastrointestinal perfusate were collected for an additional 80 min. Insulin-stimulated acid secretion peaked 60 min after bolus infusion in normal animals; a response that was significantly decreased in the diabetic rats. Similarly, 2-deoxyglucose-induced glucopenia increased gastric acid secretion to a lower extent in diabetic versus normal rats. The stimulatory response to pentagastrin was prompt and essentially equal in normal and diabetic animals. However, when hypoglycemia was prevented by glucose infusion, insulin did not stimulate gastric acid secretion in normal rats. Further, glucose infusion in these animals actually enhanced the secretory response to pentagastrin. Nitro-L-arginine methyl ester (L-NAME 20 mg/kg i.v.), an inhibitor of NO synthetase, also prevented the secretory response to insulin but not to pentagastrin. Preinfusion of arginine (100 mg/kg i.v.) in diabetic rats restored the gastric secretory response to insulin toward that of normal animals. We conclude that the gastric acid secretory response to insulin, but not to pentagastrin, is decreased in diabetic animals, that this response may operate through a NO mediated mechanism possibly set in motion by central nervous system glucopenia and that this NO-mediated mechanism is attenuated in diabetes.
 ...
PMID:Impaired insulin but normal pentagastrin effect on gastric acid secretion in diabetic rats: a role for nitric oxide. 934 40

Glucose homeostasis was studied in the spontaneously hypertensive rat (SHR). The fasting plasma glucose levels were similar in the SHR and normotensive Wistar-Kyoto (WKY) rat (102.7+/-2.4 vs. 107.4+/-4.2 mg/dl, P > 0.01). One hour after glucose challenge, the plasma glucose level was slightly but insignificantly increased in both SHR and WKY rat (117+/-2.5 vs. 114.3+/-3.2 mg/dl, P > 0.01). After N(G)nitro-L-arginine methyl ester (L-NAME) 20 mg/kg per day was administered intraperitoneally (i.p.) for 4 days, the plasma glucose level was significantly increased in the rats (SHR 167.3+/-4.9; WKY rat 136.0+/-4.8 mg/dl); the increase was significantly more pronounced in the SHR. The fasting insulin levels were similar in the SHR and WKY rats (2.3+/-0.4 vs. 2.0+/-0.3 ng/ml, P > 0.01). One hour after glucose challenge, the insulin level was significantly increased in the WKY rat (4.8+/-0.7 ng/ml) but not in the SHR (2.2+/-0.4 ng/ml). With L-NAME treatment, plasma insulin increase was noted in the WKY rat but not SHR (4.6+/-0.6 vs. 2.6+/-0.4 ng/ml, n = 8, P < 0.01). One hour after insulin 1 IU/kg was injected intramuscularly (i.m.), the plasma glucose level was significantly decreased in both the SHR (from 115.0+/-6.5 to 48.6+/-3.6 mg/dl, n = 8) and WKY rat (from 108.3+/-3.8 to 52.6+/-4.2 mg/dl, n = 8). No significant difference was noted between the decrease of the two groups (P > 0.01). The present findings suggested that NO plays a role in the glucose homeostasis of rats. NO-synthase blockade resulted in an increase of plasma glucose level. The SHR maintains normal glucose level and tolerance in spite of a defective insulin release response. This is probably due the compensatory effect of a more prominent NO-dependent glucose homeostatic function.
 ...
PMID:The role of nitric oxide in the control of plasma glucose concentration in spontaneously hypertensive rats. 935 Aug 40

This study was conducted to determine the effect of stevioside (SVS) on glucose metabolism. The experiments were performed in male Wistar rats treated with SVS either by intravenous infusion or feeding. SVS infusion (150 mg/mL) was carried out in doses of 0.67, 1.00, and 1.33 mL.kg-1 body weight.h-1. The plasma glucose level significantly increased both during and after SVS infusion, whereas it was not affected by SVS feeding (13.3 mL.kg-1 body weight). The glucose turnover rate (GTR) of [14C(U)]glucose and [3(-3)H]glucose was not significantly different between control and SVS infusion animals. Percent glucose carbon recycling and glucose clearance were reduced from 28.7 +/- 1.3 to 23.0 +/- 1.6% (p < 0.05) and from 6.46 +/- 0.34 to 4.99 +/- 0.20 mL.min-1.kg-1 body weight (p < 0.01), respectively. The plasma insulin level did not change, whereas the plasma glucose level significantly increased from 120.3 +/- 5.9 to 176.8 +/- 10.8 mg% (p < 0.01) during SVS infusion. Animals pretreated with angiotensin II and arginine vasopressin showed no significant effect, while animals pretreated with prazosin had an attenuated hyperglycemic effect of SVS infusion. Pretreatment with indomethacin or N omega-nitro-L-arginine methyl ester (L-NAME) alleviated the plasma glucose level during the second period of SVS infusion. Pretreatment with the combination infusion of indomethacin and L-NAME reduced the plasma glucose level from 117.0 +/- 1.8 to 109.0 +/- 1.7 mg% (p < 0.001), and normalized the plasma glucose level in the second period of SVS infusion. Insulin infusion inhibited the hyperglycemic effect of SVS infusion. The present results show that the elevation of the plasma glucose level during SVS infusion is not due to the reduction of the insulin level. It is probably the effect of SVS on glucose transport across the cell. Insulin response to a high plasma glucose level is suppressed during SVS infusion. Several interactions among norepinephrine, prostaglandin, and nitric oxide are involved in modulating the hyperglycemia during SVS infusion.
 ...
PMID:The effect of stevioside on glucose metabolism in rat. 936 11

We previously reported the impaired HCO3- secretion and the increased mucosal susceptibility to acid in the duodenum of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated the salutary effect of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) on these changes and compared it with those of insulin. Animals were injected streptozotocin (STZ: 70 mg/kg, ip) and used after 1, 3-4, and 5-6 weeks of diabetes with blood glucose levels of > 300 mg/dL. Under urethane anesthesia the HCO3- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. L-NAME (20 mg/kg x 2) or insulin (4 units/rat) was administered sc for 4-5 weeks, starting 1 week after STZ treatment. The duodenal HCO3- secretory responses to various stimuli such as mucosal acidification (10 mM HCl for 10 min), 16,16-dimethyl prostaglandin E2 (dmPGE2: 10 micrograms/kg, i.v.), and vagal stimulation (0.5 mA, 2 ms, 3 Hz) were significantly decreased in STZ-treated rats, depending on the duration of diabetes. Repeated administration of L-NAME, starting from 1 week after STZ treatment, significantly reduced blood glucose levels toward normal values and restored the HCO3- responses to various stimuli in STZ rats, the effects being similar to those observed after supplementation of insulin. Diabetic rats developed duodenal lesions after perfusion of the duodenum with 150 mM HCl for 4 h, but this ulcerogenic response was significantly inhibited by the repeated treatment with L-NAME as well as insulin. We conclude that L-NAME is effective in ameliorating hyperglycemic conditions in STZ-diabetic rats, similar to insulin, and restores the impaired HCO3- secretion and the increased mucosal susceptibility to acid in diabetic rat duodenums.
 ...
PMID:Impaired duodenal bicarbonate secretion in diabetic rats. Salutary effect of nitric oxide synthase inhibitor. 940 1

1. Rats develop tactile allodynia to stimulation of the plantar surface of the hindpaw with von Frey filaments within days of the onset of streptozotocin-induced diabetes. This is prevented by insulin and alleviated by systemic lignocaine, but the aetiology is unknown. 2. Using indwelling lumbar intrathecal catheters to deliver pharmacological agents, we have investigated whether tactile allodynia in streptozotocin-diabetic rats is dependent on mechanisms associated with spinal sensitization, by assessing the efficacy of agents that inhibit specific components of spinal nociceptive processing. 3. Dose-dependent inhibition of tactile allodynia in diabetic rats was noted with the N-type calcium channel antagonist SNX 239, the alpha2-adrenoceptor agonist dexmedetomidine, the mu-opioid receptor agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and the non-NMDA receptor antagonist NBQX. 4. No effect on tactile allodynia was noted after intrathecal administration of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the cyclo-oxygenase inhibitor ketorolac, the L-type calcium channel inhibitor diltiazem or any vehicle. 5. These data suggest that the tactile allodynia of diabetic rats involves spinal glutamatergic pathways but is not associated with spinal release of nitric oxide or prostaglandins.
 ...
PMID:Spinal pharmacology of tactile allodynia in diabetic rats. 942 Dec 98

1. The effects of human insulin and elevated D-glucose on L-arginine transport and synthesis of nitric oxide (NO) and prostacyclin (PGI2) have been investigated in human umbilical vein endothelial cells isolated from gestational diabetic pregnancies. 2. The increase in the Vmax for L-arginine transport (9.0 +/- 1.1) pmol (micrograms protein)-1 min-1) in diabetic endothelial cells cultured in 5 mM D-glucose was unaffected following 24 h exposure to 25 mM D-glucose. 3. Gestational diabetes-induced increases in basal intracellular cGMP and L-citrulline levels (inhibitable by L-NAME) and [Ca2+], were unaffected by elevated D-glucose. In contrast, PGI2 release was inhibited in diabetic cells exposed to either 5 or 25 mM D-glucose. 4. Elevated D-glucose attenuated histamine (10 microM, 5 min)-stimulated accumulation of cGMP and L-citrulline in endothelial cells isolated from gestational diabetic pregnancies. 5. The membrane hyperpolarization (-79 +/- 0.9 mV) sustained in diabetic endothelial cells in culture was insensitive to elevated D-glucose. 6. Elevated D-glucose abolished the stimulatory effect of human insulin (1 nM, 8 h) on L-[3H]leucine incorporation in diabetic endothelial cells cultured in 5 mM D-glucose. 7. Human insulin reduced the elevated rates of L-arginine transport and cGMP accumulation in diabetic cells cultured in 5 mM D-glucose but failed to reduce increased rates of transport or NO production in cells exposed to 25 mM D-glucose or cycloheximide. 8. Our findings demonstrate that hyperglycaemia impairs the actions of human insulin on umbilical vein endothelial cells isolated from gestational diabetic pregnancies. Changes in insulin sensitivity and/or its signalling cascade may be affected by hyperglycaemia associated with gestational diabetes, resulting in insulin resistance in endothelial cells derived from the fetal vasculature.
 ...
PMID:Elevated D-glucose induces insulin insensitivity in human umbilical endothelial cells isolated from gestational diabetic pregnancies. 948 83

ATP-dependent potassium channel blockers used as hypoglycaemic agents may have effects on vascular disease in diabetes mellitus beyond their effect on blood glucose control. This study was designed to determine the effects of treatment with gliclazide on the isolated abdominal aorta of diabetic rabbits in which endothelium-dependent relaxation is impaired by a mechanism involving oxygen-derived free radicals. After induction of diabetes with alloxan, there was no effect of gliclazide (10 mg x kg(-1) day(-1) orally) on blood glucose or insulin levels over a 6 week period. Hence, this permitted an examination of the vascular effects of gliclazide in diabetic rabbits exclusive of metabolic effects. Acetylcholine- and nitric oxide-induced relaxation in aortae from rabbits treated with or without gliclazide were measured in the absence or presence of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (L-NAME). Diabetes was associated with significant impairment of acetylcholine-induced endothelium-dependent relaxation of the abdominal aorta which was not significant in diabetic rabbits treated with gliclazide in vivo. Aortae from diabetic rabbits studied in the presence of L-NAME showed an exaggerated contraction to acetylcholine which was prevented in rabbits treated with gliclazide. Gliclazide treatment did not affect the response to acetylcholine of normal rabbit aorta, and gliclazide when added in vitro had no effect on the response of diabetic rabbit aorta, suggesting that the effect of gliclazide was specific to the abnormality arising with diabetes and was not due to an acute effect of the drug. These data indicate that gliclazide, aside from either a direct antioxidant action or an effect on insulin or glucose levels, may ameliorate diabetic endothelial cell dysfunction.
 ...
PMID:Vascular action of the hypoglycaemic agent gliclazide in diabetic rabbits. 949 23

To evaluate the role of nitric oxide synthase (nNOS) in the pathogenesis of diabetic neuropathy, we investigated nociception and nNOS expression in dorsal root ganglion (DRG) of rats with streptozocin-induced diabetes. Paw withdrawal threshold to noxious mechanical stimuli was decreased in both L-NAME-treated and diabetic rats. The number of NADPH-diaphorase positive neurons was significantly decreased in untreated diabetic compared with control rats. Decreased expression of nNOS protein was confirmed by immunoblotting. Insulin treatment completely prevented decreases in withdrawal threshold and nNOS expression. Cyclic GMP content paralleled nNOS expression in experimental animals. These results suggest that decreased nNOS-cGMP system in DRG may play a role in the pathogenesis of diabetic sensory neuropathy.
 ...
PMID:Hyperalgesia and decreased neuronal nitric oxide synthase in diabetic rats. 950 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>