Pathology of Autonomic Neuropathy in Diabetes Mellitus

Duchen, L. W.; Anjorin, AO; Watkins, P J; Mackay, J. D.

doi:10.7326/0003-4819-92-2-301

Cited by 238 publications

(133 citation statements)

References 6 publications

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“…In human type I diabetes 30 and in STZ-diabetic rats, there are reports of the presence of giant axons, and of the presence of aggregates of intra-axonal subcellular organelles. [31][32][33] There are also observations of some regenerative activity in diabetic nerves. [34][35][36] Becker et al (2000) 6 compared the concentrations of NA and adrenaline in cavernous and systemic blood during penile erection in humans, and found a significant reduction of NA in cavernous blood, while adrenaline levels rose in peripheral and cavernous blood during developing erection.…”

Section: Discussionmentioning

confidence: 92%

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

et al. 2007

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The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (Po0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.

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Section: Discussionmentioning

confidence: 92%

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

et al. 2007

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“…Autonomic neuropathy is a severe and crippling complication of T1D of long duration; recent evidences indicate that immune pathogenesis plays an important role in this complication [12][13][14][15]. Lymphocytes and plasma cells infi-ltrate autonomic ganglia and nerve bundles [13], and in the circulation, activated T-cells [14] and complement breakdown products [15] are present at elevated levels.…”

Section: Introductionmentioning

confidence: 99%

“…Lymphocytes and plasma cells infi-ltrate autonomic ganglia and nerve bundles [13], and in the circulation, activated T-cells [14] and complement breakdown products [15] are present at elevated levels. It is well reported that autoantibodies to nervous tissues were found in T1D neuropathic patients, but not in patients with T1D of similar duration but without complications [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Farhan¹,

Alghasham²,

Zafar³

et al. 2013

J Diab Res Clin Met

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Background: Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease with autoantibodies against glutamic-aciddecarboxylase (GAD)65, insulin and tyrosine phosphatase (TP) as a feature of disease. The correlations of these autoantibodies with disease severity remain to be explored. Here we investigate the status and contribution of autoantibodies against GAD65, insulin and TP in T1D patients and to explore whether these antibodies have a role in T1D progression and in T1D associated neuropathy. Methods: Sera from 57 T1D patients with varying levels of disease activities and 42 age-and sex-matched healthy controls were evaluated for anti-GAD65-antibodies, anti-insulin-antibodies and anti-TP-antibodies. Results: Serum analysis showed T1D patients contain 42% of anti-GAD65-antibodies, 76% of anti-insulin-antibodies and 34% of anti-TP-antibodies. Interestingly, not only was there an increased number of subjects positive for these antibodies, but also levels of these antibodies were significantly higher among T1D patients whose ages were >35 years as compared with younger T1D patients (age ≤35 years). In addition, significant correlation was observed between the levels of these antibodies and glycosylated haemoglobin (HbA 1c ). Furthermore, T1D neuropathic patients had higher levels of these antibodies compared with T1D patients without neuropathy. Conclusions: Our data support an association between these markers autoantibodies and severity of T1D. The stronger response observed in patients with uncontrolled T1D suggests that these antibodies may be useful biomarkers in evaluating the progress of T1D and in elucidating the mechanisms of disease pathogenesis.

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“…The gastrointestinal system is one of the commonly affected systems where the vagus nerve usually shows signs of demyelination [1][2][3] and degeneration of myelinated fibres, axonal terminals and dendrites [2][3][4][5][6]. Gastric dysfunctions (diabetic gastropathies) associated with diabetic vagal lesion range from, tachygastria, antral hypomotility, and frank gastroparesis to abnormal myoelectric activities.…”

Section: Introductionmentioning

confidence: 99%

Impairment of transneuronal traffic in Streptozotocin-induced diabetes, a WGA-HRP neurohistochemical study in the rat

Odekunle

2006

J Biomed Sci

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Retrograde transport of Wheat germ agglutinin conjugated to Horseradish peroxidase (WGA-HRP) was used in labeling vagal neurons projecting to the stomach from the dorsal motor nucleus of the vagus nerve (DMNV) in Streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in the experimental rats by intraperitoneal injection of buffered STZ. Control rats were injected with an equivalent volume of the citrate buffer not containing STZ.The experimental rats, which became diabetic about 24 h after intraperitoneal injection of STZ, were kept alive for a period of 24 weeks to attain a chronic state of diabetes. Control euglycaemic rats were also kept alive for 24 weeks. At the end of 24 weeks, the two groups of rats were prepared for stomach surgery. Following anaesthesia laparotomy was performed and the stomach exteriorized. The anterior and posterior walls of the stomach were injected with 0.1 ml of 5% WGA-HRP in 0.5 M sodium chloride. Experimental and control rats were sacrificed 48-72 h after tracer injection by transcardial perfusion with normal saline, fixative and buffered sucrose.Transverse serial frozen sections of the brainstem were processed for WGA-HRP neurohistochemistry and analyzed under light and dark-field microscopy. The analyses of the sections taken from the chronic diabetic rats revealed fewer WGA-HRP labeled neurons in the DMNV than sections taken from the control euglycaemic rats. The depletion of labeled neurons in the diabetic rats compared with the euglycaemic rats is indicative of an interference with the mechanism of retrograde neuronal transport of WGA-HRP by chronic diabetic state.

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Pathology of Autonomic Neuropathy in Diabetes Mellitus

Cited by 238 publications

References 6 publications

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

Impact of anti-glutamic acid decarboxylase-65, anti-insulin and anti-tyrosine phosphatase autoantibodies on disease activity in type 1 diabetes patients

Impairment of transneuronal traffic in Streptozotocin-induced diabetes, a WGA-HRP neurohistochemical study in the rat

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