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

Impaired endothelium-dependent relaxation of blood vessels is a common feature in diabetes, but the exact underlying mechanisms have not yet been clarified. In present study, endothelium-dependent vasorelaxation of aortic rings were evaluated in vitro in streptozotocin (STZ)-induced diabetic and age-matched control rats. Moreover, nitric oxide synthase (NOS) activity of aortic endothelial cells was assessed in both diabetic and healthy rats using histochemical staining for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity. The results showed a significant decrease of endothelium-dependent relaxation in response to acetylcholine (ACh) in diabetic rings, compared with controls, that was accompanied by a remarkable attenuation of NOS activity in diabetic sections of rat aorta stained for NADPH-diaphorase. Furthermore, a membrane disruption of some endothelial cells was also observed in all diabetic sections. It can be concluded that a decrease in NOS activity together with a disruption of endothelial cell membrane play a major role in endothelial dysfunction observed in diabetes.
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PMID:Histochemical assessment of nitric oxide synthase activity in aortic endothelial cells of streptozotocin-induced diabetic rats. 1464 5

Diabetes is an endocrine and metabolic disorder often associated with erectile dysfunction and peripheral neuropathy. Among other factors, penile erection is induced by activation of nitric oxide synthase (NOS). Hypothalamic paraventricular nuclei neurons produce NO and project to spinal cord areas implicated in penile reflexes. These nuclei have shown an increase of NOS in streptozotocin-induced diabetic rats. NOS-containing neurons are identical to the populations of neurons selectively stained for NADPH-diaphorase activity. Using this technique, we have evaluated changes of NOS in the lumbar spinal cord of diabetic rats with or without insulin treatment. Positive staining was found in motoneurons, dorsal horn neurons (layer II), neurons surrounding the ependimus (layer X) and neurons at the intermediolateral cell column (ILCC). Diabetic animals showed significant decrease in reactive area and increase of the histochemical reaction in motoneurons from the sexual dimorphic nuclei and in neurons of the ILCC. A marked decrease of the number of reactive neurons was also observed in layer II. Morphologic alterations were observed in neurons of layer X as an increase in the percentage of multipolar neurons and a decrease in the number and length of secondary processes. The alterations observed in these animals were absent in the insulin treated diabetic animals. These results show the plasticity of lumbar spinal cord neurons, suggesting a direct participation of NO synthesis in the physiopathology of the erection dysfunction in diabetes.
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PMID:Changes of NADPH-diaphorase reactivity in lumbar spinal cord of short-term streptozotocin induced diabetic rats. 1470 71

Nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS). Alternation of NOS expression is implicated in the pathogenesis of numerous secondary complications of diabetes. Aqueous extract of Ginseng radix has traditionally been used for the various disorders including diabetes. In this study, the effect of Ginseng radix on the NOS expression in the hippocampus of streptozotocin (STZ)-induced diabetic rats was investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Enhanced NOS expression was detected in the hippocampus of diabetic rats and administration of Ginseng radix suppressed NOS expression. Ginseng radix may aid the treatment of central nervous system complications in diabetes.
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PMID:Administration of Ginseng radix decreases nitric oxide synthase expression in the hippocampus of streptozotocin-induced diabetic rats. 1548 40

The influence of diabetes mellitus on brain pathology is increasingly recognized. Previous contributions of our laboratory demonstrated in models of type 1 diabetes (nonobese diabetic and streptozotocin (STZ)-treated mice), a marked astrogliosis and neurogenesis deficit in hippocampus and increased expression of hypothalamic neuropeptides. In the present investigation, we further analyzed alterations of astroglia and neurons in the hippocampus of mice 1 month after STZ-induced diabetes. Results showed that these STZ-diabetic mice presented: (a) increased number of astrocytes positive for apolipoprotein-E (Apo-E), a marker of ongoing neuronal dysfunction; (b) abnormal expression of early gene products associated with neuronal activation, including a high number of Jun + neurons in CA1 and CA3 layers and dentate gyrus, and of Fos-expressing neurons in CA3 layer; (c) augmented activity of NADPH-diaphorase, linked to oxidative stress, in CA3 region. These data support the concept that uncontrolled diabetes leads to hippocampal pathology, which adjoin to changes in other brain structures such as hypothalamus and cerebral cortex.
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PMID:Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes. 1574 69

The NADPH-diaphorase (NADPH-d) positive myoenteric neurons from the body of the stomach of rats with streptozotocin-induced diabetes with or without supplementation with acetyl-L-carnitine (ALC) were evaluated. At the age of 105 days the animals were divided into four groups: normoglycaemic (C), normoglycaemic supplemented with ALC (CC), diabetic (D) and diabetic supplemented with ALC (DC). The supplementation with ALC (200 mg/kg body weight/day) to groups CC and DC was made during 105 days. After this period the animals were killed and the stomach removed and subjected to the histochemical technique of NADPH-d for the staining of the neurons of the myoenteric plexus. The area of 500 neurons of each group was investigated, as well as the neuronal density in an area of 23.84 mm(2) in each stomach. ALC promoted reduction (P < 0.05) of fasting glycaemia, water ingestion and areas of the profiles of the cell bodies of the NADPH-d neurons in the diabetic animals. The density of these neurons was not statistically different in the groups studied. It is suggested, therefore, a moderate neuroprotective effect of ALC, because the diminishment of the areas of the neuronal profiles in the supplemented diabetic animals, although being statistically significant relative to the non-supplemented diabetics, was not sufficient to equal the values from the non-diabetic controls.
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PMID:Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-L-carnitine. 1577 70

Summary In this study we investigated the effect of the acetyl-L-carnitine (ALC) supplementation on the myenteric neurons of the jejunum of rats made diabetic at the age of 105 days by streptozotocin (35 mg/kg body weight). Four groups were used: non-diabetic (C), non-diabetic supplemented with ALC (CC), diabetic (D), diabetic supplemented with ALC (DC). After 15 weeks of diabetes induction the blood was collected by cardiac puncture to evaluate glycaemia and glycated haemoglobin. Next the animals were killed and the jejunum was collected and subjected to whole-mount preparation to evidence the myenteric neurons through the histochemical technique of the NADH-diaphorase. The neuronal counts were made in 80 microscopic fields, in tissue samples of five animals of each group. The profiles of the cell bodies of 1000 neurons per group were analysed. Diabetes induced a significant increase in the area of the cell body and decrease in the number of NADH-diaphorase positive myoenteric neurons. ALC suplementation to the diabetic group promoted smaller hypertrophic effects and less neuronal loss than in the myoenteric neurons of the diabetic rats, and in addition diminished the body weight decrease and reduced the fasting glycaemia.
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PMID:Morphometric and quantitative evaluation of the NADH-diaphorase positive myenteric neurons of the jejunum of streptozotocin-diabetic rats supplemented with acetyl-L-carnitine. 1592 29

Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastructural changes in myocardial capillary endothelium in two models of heart failure streptozotocin-induced diabetes mellitus (STZ) and NO-deficient hypertension in male Wistar rats. Diabetes was induced by a single i.v. dose of STZ (45 mg/kg) and chronic 9-week stage was analysed. To induce NO-deficient hypertension, animals were treated with inhibitor of NO synthase L-nitroarginine methylester (L-NAME) (40 mg/kg) for 4 weeks. Left ventricular tissue was processed for enzyme catalytic histochemistry of capillary alkaline phosphatase (AlPh), dipeptidyl peptidase IV (DPP IV), and endothelial NO synthase/NADPH-diaphorase (NOS) and for ultrastructural analysis. In diabetic and hypertensive rats, lower/absent AlPh and DPP IV activities were found in focal micro-areas. NOS activity was significantly reduced and persisted only locally. Quantitative evaluation demonstrated reduction of reaction product intensity of AlPh, DPP and NOS by 49.50%, 74.36%, 20.05% in diabetic and 62.93%, 82.71%, 37.65% in hypertensive rats. Subcellular alterations of endothelial cells were found in heart of both groups suggesting injury of capillary function as well as compensatory processes. Endothelial injury was more significant in diabetic animals, in contrast the adaptation was more evident in hypertensive ones. CONCLUDING: both STZ-induced diabetes- and NO-deficient hypertension-related cardiomyopathy were accompanied by similar features of structural remodelling of cardiac capillary network manifested as angiogenesis and angiopathy. The latter was however, predominant and may accelerate disappearance of capillary endothelium contributing to myocardial dysfunction.
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PMID:Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension. 1604 16

Recent evidence suggests that a central mechanism may be contributing to the sympathetic abnormality in diabetes. Nitric oxide (NO) has been known as a neurotransmitter in the central nervous system. The goal of this study was to examine the role of the endogenous NO system of the paraventricular nucleus (PVN) in regulation of renal sympathetic nerve activity (RSNA) in streptozotocin (STZ)-induced diabetic rats. The change in number of NADPH-diaphorase-positive neurons [a marker for neuronal NO synthase (nNOS) activity] in the PVN was measured. Diabetic rats were found to have significantly fewer nNOS positive cells in the PVN than in the control group (120 +/- 11 vs. 149 +/- 13, P < 0.05). Using RT PCR, Western blotting and immunofluorescent staining, it was also found that nNOS mRNA expression and protein level in the PVN were significantly decreased in the diabetic rats. Furthermore, using an in vivo microdialysis technique, we found that there was a lower NO(x) release from the PVN perfusates in rats with diabetes compared with the control rats (142 +/- 33 nM vs. 228 +/- 29 nM, P < 0.05). In alpha-chloralose- and urethane-anesthetized rats, an inhibitor of NO synthase, l-NMMA, microinjected into the PVN produced a dose-dependent increase in RSNA, mean arterial pressure (MAP), and heart rate (HR) in both control and diabetic rats. These responses were significantly attenuated in rats with diabetes compared with control rats (RSNA: 11 +/- 3% vs. 35 +/- 3%, P < 0.05). On the other hand, an NO donor, sodium nitroprusside (SNP), microinjected into the PVN produced a dose-dependent decrease in RSNA, MAP, and HR in the control and diabetic rats. RSNA (17 +/- 3%, vs. 41 +/- 6%, P < 0.05) and MAP in response to SNP were significantly blunted in the diabetic group compared with the control group. In conclusion, these data indicate an altered NO mechanism in the PVN of diabetic rats. This altered mechanism may contribute to the increased renal sympathetic neural activity observed in diabetes.
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PMID:Blunted nitric oxide-mediated inhibition of sympathetic nerve activity within the paraventricular nucleus in diabetic rats. 1632 52

Diabetes-induced erectile dysfunction is one of the most prevalent complications of diabetes in males. alpha-Lipoic acid (ALA) and its reduced form, dihydrolipoic acid, are powerful antioxidants. Data strongly suggest that, because of its antioxidant properties, ALA is particularly suited to the prevention and/or treatment of diabetic complications that arise from overproduction of reactive oxygen and nitrogen. The aim of this study was to investigate the localization of nitric oxide synthetase (NOS) in normal and diabetic rat cavernous smooth muscles and to examine the effects of ALA on them. Rats were divided into four groups: control, diabetic, diabetic plus ALA, and ALA only. Penile tissues were taken 15 days after drug application and examined histochemically and immunohistochemically. Comparison of the control and diabetic groups revealed that the axons of nerve cells were not identified with Masson trichrome in the diabetic group, whereas in the control group NOS localization and immunostaining (endothelial NOS [eNOS]) were normal. Diabetic rats administered ALA showed improvement in Masson trichrome, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and eNOS localization compared with untreated diabetic rats. Although there was no difference between the control group and the group administered ALA only, we observed an increase in NADPH-d and eNOS. In erection, eNOS and neuronal NOS (nNOS) may have a significant role. In pathologic conditions, erectile dysfunction may occur as a result of an increase in inducible macrophage-type NOS (iNOS). ALA plays an important role in treatment of erectile dysfunction by decreasing iNOS and increasing other isoforms of NOS.
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PMID:The effects of alpha-lipoic acid on nitric oxide synthetase dispersion in penile function in streptozotocin-induced diabetic rats. 1637 81

In this work, we investigated the effect of the acetyl-L-carnitine (ALC) supplementation (200 mg/kg/day) on the myenteric neurons of the ileum of rats made diabetic by streptozotocin (35 mg/kg, i.v.). Four groups were used: diabetic (D), diabetic supplemented with ALC (DC), control (C) and control supplemented with ALC (CC). After 15 weeks of diabetes induction the animals were killed and the ileum was collected and subjected to whole-mount preparation to evidence the myenteric neurons through the histochemical technique of the NADH-diaphorase. The density of neurons seen in 12.72 mm2 of ileum showed no difference among the groups, although in group D it was 22% smaller than in group C, while group DC was 9% smaller to group CC. The profiles of the cell bodies (PC) of 1000 neurons per group were analysed. The neurons PC in group D decreased (P < 0.0001) when compared with other groups and increased (P < 0.0001) when compared with group DC. The incidence of neurons with a PC inferior to 200 microm2 was larger in group D. The frequency of neurons with a PC higher than 200 microm2 in group DC was close to those seen in groups C and CC. We concluded that ALC eases the loss of neurons and makes the incidence of myenteric neurons with a PC higher than 200 microm2 similar to the control rats.
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PMID:Morphoquantitative aspects of NADH-diaphorase myenteric neurons in the ileum of diabetic rats treated with acetyl-L-carnitine. 1643 67


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