Enteric nerves in diabetic rats: Increase in vasoactive intestinal polypeptide but not substance P

Belai, Abebech; Lincoln, J.; Milner, P.; Crowe, R.; Loesch, Andrzej; Burnstock, Geoffrey

doi:10.1016/0016-5085(85)90195-7

Cited by 121 publications

(57 citation statements)

References 31 publications

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“…The diabetes-induced changes in NA-, NOS-, VIP-, and CGRP-containing nerves supplying the ileum were similar to those reported previously (22,40,41). There is evidence that VIP-and NA-containing nerves are degenerating at this stage, whereas changes in CGRP-containing nerves reflect loss of neurotransmitter expression rather than nerve fiber loss (4,5,42,43).…”

Section: Diabetic Autonomic Neuropathy Preventionsupporting

confidence: 89%

The Effectiveness of Treatments of Diabetic Autonomic Neuropathy Is Not the Same in Autonomic Nerves Supplying Different Organs

2003

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The aim of the study was to investigate antioxidant (␣-lipoic acid [LA]) and ␥-linolenic acid treatments in the prevention of changes in autonomic nerves induced in streptozotocin-diabetic rats. Autonomic nerves supplying the heart, penis, and gut were examined using immunohistochemical and biochemical techniques. LA and ␥-linolenic acid (present in evening primrose oil [EPO]) were administered as dietary supplements (ϳ80 and 200 mg ⅐ kg ؊1 ⅐ day ؊1 , respectively). LA treatment prevented the diabetes-induced decrease of norepinephrine (NA) in the heart and of type I nitric oxide synthase (NOS-I) expression in erectile tissue of the penis but failed to prevent diabetes-induced changes in NA-, vasoactive intestinal polypeptide-, or calcitonin gene-related peptide-containing nerves supplying the ileum. LA partially prevented and EPO totally prevented the increase in NOS-I activity induced by diabetes in the ileum. EPO treatment failed to prevent any other diabetes-induced changes in the heart, penis, or ileum. These results demonstrate that, whereas LA treatment is more effective than EPO in preventing diabetes-induced changes in autonomic nerves, the effectiveness of LA treatment varies with the target organ studied. Diabetes-induced changes in nerves supplying the ileum are more resistant to treatment than those of the heart and penis. Diabetes 52:157-164, 2003

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Section: Diabetic Autonomic Neuropathy Preventionsupporting

confidence: 89%

The Effectiveness of Treatments of Diabetic Autonomic Neuropathy Is Not the Same in Autonomic Nerves Supplying Different Organs

2003

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“…Of these, enteric neuropathy may be particularly important (5,6,48). Several studies of animal models of diabetes have convincingly shown disturbances in enteric nerves, particularly involving nitrergic nerves (14,49,52).…”

Section: Discussionmentioning

confidence: 99%

Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum

Gangula

Maner

Micci

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

100

150

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Gangula PRR, Maner WL, Micci M-A, Garfield RE, Pasricha PJ. Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J Physiol Gastrointest Liver Physiol 292: G725-G733, 2007; doi:10.1152/ajpgi.00406.2006.-Diabetic gastroparesis is a disorder that predominantly affects women. However, the biological basis of this sex bias remains completely unknown. In this study we tested the hypothesis that a component of this effect may be mediated by the nitrergic inhibitory system of the enteric nervous system. Agematched male and female Sprague-Dawley rats were studied 8 or 12 wk after streptozotocin (55 mg/kg body wt ip)-induced sustained hyperglycemia and compared with controls. Solid gastric emptying (GE) studies were performed in all the groups. Changes in gastric antrum neuronal nitric oxide synthase (nNOS) mRNA and protein levels were analyzed by real-time PCR and Western immunoblotting, respectively. nNOS dimerization studies were performed using lowtemperature SDS-PAGE. In vitro nitrergic relaxation (area under curve/mg tissue wt) was studied after the application of electric field stimulation in an organ bath. Changes in intragastric pressure (mmHg⅐s) in freely moving rats in the presence or absence of N Gnitro-L-arginine methyl ester (nitric oxide synthase inhibitor) were examined by an ambulatory telemetric method. After diabetes induction, GE is delayed in both male and female rats. However, diabetic females exhibited significant delayed GE than in diabetic males. Compared with male controls, gastric nNOS expression and nitrergic relaxation were substantially elevated in healthy female control rats, accompanied by significantly reduced intragastric pressure. The active dimeric form and dimer-to-monomer ratio of nNOS␣ were also higher in healthy females compared with male rats (P Ͻ 0.05). Diabetic females, but not males, showed significant (P Ͻ 0.05) impairment in both gastric nNOS␣ dimerization and nitrergic relaxation, accompanied by an increase in intragastric pressure. Our data provide evidence that females may have a greater dependency on the nitrergic mechanisms in health. Furthermore, diabetes seems to affect the nitrergic system to a greater extent in females than in males. Together, these changes may account for the greater vulnerability of females to diabetic gastric dysfunction.solid gastric emptying; nitrergic relaxation; intragastric pressure GASTRIC DYSMOTILITY OR GASTROPATHY occurs in 20 -55% of patients with Type 1 (insulin dependent) and up to 30% of patients with Type 2 diabetes (non-insulin dependent) (37). Symptoms of diabetic gastropathy can range from mild dyspepsia to recurrent vomiting and abdominal pain and are often associated with delayed or accelerated gastric emptying. Fundic tone abnormalities and/or poor antroduodenal coordination has been reported in diabetic patients (28). Although the pathogenesis of diabetic gastropathy is not completely understood, it appears to be much more common (up to four times) in w...

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“…Systematization of the studies on the enteric neurons, especially those of the myenteric plexus of species such as the rat, mouse and guinea-pig, have permitted to determine, with relative precision, the functions of specific groups of neurons [7][8][9] . Due to the accessibility of the ENS, investigations about the alterations caused by pathophysiological states, such as diabetes, have been equally productive; there are reports on the literature [10][11][12][13] about the differential effects of diabetes on specific neurotransmitter systems and on neurons of diverse intestinal segments.…”

Section: Palavras-chave: Duodeno Neurônios Mientéricos Diabetes Agumentioning

confidence: 99%

Number and size of myenteric neurons of the duodenum of adult rats with acute diabetes

Furlan

Miranda-Neto

Sant’Ana

et al. 1999

Arq. Neuro-Psiquiatr.

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-This study had as its purpose to assess the effects of acute diabetes induced by streptozotocin (35 mg/kg body weight) on the number and size of the myenteric neurons of the duodenum of adult rats considering equally the antimesenteric and intermediate regions of the intestinal circumference. Experimental period extended for a week. Neuronal counts were carried out on the same number of fields of both regions of the duodenal circumference and measurements of neuronal and nuclear areas on equal numbers of cells. Number and size of the myenteric neurons stained with Giemsa were not significantly different between groups. On the other hand, the proportion of NADH-positive neurons increased from 18.54% on the controls to 39.33% on the diabetics. The authors discuss that this increased reactivity probably results from a greater NADH/NAD + ratio, described in many tissues of diabetic animals, which has consequences on the modulation of the enzymes that use these cofactors and whose activity is detected by the NADH-diaphorase technique.KEY WORDS: duodenum, myenteric neurons, acute diabetes, NADH-diaphorase.Número e tamanho dos neurônios mientéricos do duodeno de ratos adultos com diabetes agudo RESUMO -Este estudo teve como objetivo avaliar os efeitos do diabetes agudo induzido por estreptozootocina (35 mg/kg de peso corporal) sobre o número e tamanho dos neurônios mientéricos do duodeno de ratos adultos considerando de forma equivalente as regiões antimesentérica e intermediária da circunferência intestinal. O período experimental se estendeu por uma semana. As contagens neuronais foram feitas em igual número de campos nas duas regiões da circunferência duodenal e as mensurações das áreas neuronais e nucleares em igual número de células. O número e o tamanho dos neurônios corados por Giemsa não foram significativamente diferentes entre os grupos. Por outro lado, a proporção de neurônios NADH-positivos aumentou de 18,54% nos animais controles para 39,33% nos diabéticos. Os autores discutem que essa maior reatividade possivelmente resultou do aumento da proporção NADH/NAD + , descrita em diversos tecidos de animais diabéticos, que repercute na modulação das enzimas que utilizam esses cofatores e cuja atividade é detectada pela técnica da NADHdiaforase. PALAVRAS-CHAVE: duodeno, neurônios mientéricos, diabetes agudo, NADH-diaforaseThe knowledge about the mammalian enteric nervous system (ENS) can be considered, currently, as wide and in some instances, quite deep. Descriptions found on the literature assess several aspects of this subdivision of the autonomic nervous system 1-5 and reveal the richness of structure and organization of this neuronal population of magnitude similar to that of the spinal Trabalho

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Enteric nerves in diabetic rats: Increase in vasoactive intestinal polypeptide but not substance P

Cited by 121 publications

References 31 publications

The Effectiveness of Treatments of Diabetic Autonomic Neuropathy Is Not the Same in Autonomic Nerves Supplying Different Organs

The Effectiveness of Treatments of Diabetic Autonomic Neuropathy Is Not the Same in Autonomic Nerves Supplying Different Organs

Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum

Number and size of myenteric neurons of the duodenum of adult rats with acute diabetes

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