vasoactive-intestinal-peptide and Diabetic-Neuropathies

Topics: Adrenocorticotropic Hormone; Adult; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Erectile Dysfunction; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteinizing Hormone; Male; Melanocyte-Stimulating Hormones; Middle Aged; Prolactin; Reproduction; Sexual Dysfunction, Physiological; Thyrotropin-Releasing Hormone; Urodynamics; Vasoactive Intestinal Peptide

Cardiovascular autonomic neuropathy (CAN) is a relatively common and detrimental complication of diabetes mellitus (DM). Dysregulation of neuropeptides, such as calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP), are thought to play significant roles in diabetes-related cardiovascular disease. Accumulating evidence indicates the neuroprotective effects of granulocyte-colony stimulating factor (G-CSF) in different neurological disorders. The purpose of the study is to investigate the role of CGRP and VIP and possible effects of G-CSF on CAN in type I DM model in rats.. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) for 14 rats. Seven rats served as controls and 6 rats were administered G-CSF alone. DM group was randomly divided into 2 groups and received either 1mL/kg saline (DM+saline group) or 100 μg/kg/day G-CSF (DM+G-CSF group) for 4 weeks. Following electrocardiography (ECG), GCRP and VIP levels were measured in plasma samples.. Diabetes promoted a significant prolongation in the corrected QT interval (cQT) (P<0.001) whereas G-CSF administration significantly shortened cQT interval (P<0.05). Plasma VIP and CGRP levels of saline treated DM group were significantly lower than those of control group (P<0.05). G-CSF treatment significantly prevented the reduction in plasma VIP and CGRP levels (P<0.01 and P<0.05, respectively). Also, correlation analysis showed a significant negative correlation between the cQT and neuropeptide levels.. This study suggests that G-CSF can be effective in CAN by means of neuroprotection, and plasma VIP and CGRP levels can be used for the assessment of autonomic and sensory functions in diabetes.

Topics: Animals; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Neuropathies; Granulocyte Colony-Stimulating Factor; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Streptozocin; Vasoactive Intestinal Peptide

Using a stereologic approach, the density of nerve fibers innervating sweat gland (SG) fragments in patients with diabetes mellitus (DM) and healthy controls using protein gene product (PGP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) was measured to determine which marker best detected differences between the groups. Factors associated with SG nerve fiber (SGNF) innervation were assessed and the change in SG innervation over a 1-year time period was determined.. Ninety-two control subjects and 2 groups of subjects with DM totaling 97 were assessed in this cross-sectional study. Intraepidermal nerve fiber density and SG innervation were determined from leg skin biopsies that were immunohistochemically stained for ubiquitin hydrolase, VIP, and TH. Factors associated with SG innervation were assessed and 15 subjects were longitudinally followed for 1 year.. SGNF innervation was reduced in subjects with DM compared with controls. Lower SG innervation values were associated with increasing glycated hemoglobin A1c, body mass index (BMI), men compared with women, and tobacco use, but not diabetes type or age. Sex, A1c, and BMI remained significant in multivariate modeling. SG innervation measured by VIP+ fibers is a more sensitive marker for neuropathy than either PGP or TH. Fifteen subjects with DM followed for 1 year showed a significant decrease in SGNF innervation but not intraepidermal nerve fiber density.. Stereologic measurement of SG innervation is feasible to assess postganglionic autonomic nerve fiber densities. SG innervation was reduced in subjects with DM compared with control subjects and was associated with sex, A1c, and BMI in multivariate modeling. VIP+ SGNF is more severely reduced in DM than TH+ or PGP9.5+-based assessments. Progression of diabetic polyneuropathy was detected by SGNF over a 1-year time period.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cross-Sectional Studies; Diabetic Neuropathies; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Male; Middle Aged; Nerve Fibers; Sweat Glands; Tyrosine 3-Monooxygenase; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide; Young Adult

Abnormal sensations such as pain and impairment of taste are symptoms of approximately 10% of patients having diabetes mellitus.. The aim of the study was to investigate and quantify the different neuropeptide containing nerve fibres in the vallate papilla of the diabetic rat.. Immunohistochemical methods were used to study the changes of the number of different neuropeptide containing nerve terminals located in the vallate papillae in diabetic rats. Diabetes was induced in the rats with streptozotocin.. Two weeks after streptozotocin treatment the number of the substance P, galanin, vasoactive intestinal polypeptide and neuropeptide Y immunoreactive nerve terminals was significantly increased (p<0.05) in the tunica mucosa of the tongue. The number of the lymphocytes and mast cells was also increased significantly. Some of the immunoreactive nerve terminals were located in the lingual epithelium both intragemmally and extragemmally and were seen to comprise dense bundles in the lamina propria just beneath the epithelium. No taste cells were immunoreactive for any of the investigated peptides. Vasoactive intestinal polypeptide and neuropeptide Y immunoreactive nerve fibres were not detected in the taste buds. For weeks after streptozotocin administration the number of the substance P, calcitonin gene related peptide and galanin immunoreactive nerve terminals was decreased both intragemmally and intergemmally. In case of immediate insulin treatment, the number of the immunoreactive nerve terminals was similar to that of the controls, however, insulin treatment given 1 week later to diabetic rats produced a decreased number of nerve fibers. Morphometry revealed no significant difference in papilla size between the control and diabetic groups, but there were fewer taste buds (per papilla).. Increased number of immunoreactive nerve terminals and mast cells 2 weeks after the development of diabetes was the consequence of neurogenic inflammation which might cause vasoconstriction and lesions of the oral mucosa. Taste impairment, which developed 4 weeks after streptozotocin treatment could be caused by neuropathic defects and degeneration or morphological changes in the taste buds and nerve fibres.

Topics: Animals; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Galanin; Hypoglycemic Agents; Immunohistochemistry; Insulin; Lymphocyte Count; Male; Mast Cells; Nerve Endings; Neuropeptide Y; Rats; Rats, Inbred Strains; Streptozocin; Substance P; Taste Buds; Time Factors; Vasoactive Intestinal Peptide

Diabetes has a differential effect on different subpopulations of myenteric neurons. Our aim was to investigate an in vitro model to examine the pathways underlying the development of nerve changes in diabetes.. The proportions of neuronal cell bodies containing vasoactive intestinal polypeptide (VIP), neuronal nitric oxide synthase (nNOS) and calbindin relative to the pan-neuronal marker HuC/D were quantified in wholemount preparations of the myenteric plexus of adult rat ileum using double labeling immunohistochemistry. Preparations were maintained in culture for 24 h in the presence and absence of stimuli mimicking the diabetic environment including oxidative stress, carbonyl stress, high glucose and advanced glycation end products (AGEs). Data were compared with the effect of streptozotocin-induced diabetes in vivo. KEY RESULTS Only oxidative stress in vitro produced the same pattern as observed in diabetes with an increase in VIP-, decrease in nNOS-, and no change in calbindin-positive neurons. Carbonyl stress and high glucose caused an increase in VIP-containing neurons without affecting nNOS expression. In contrast, exposure to AGEs only caused a decrease in nNOS-positive neurons. Calbindin expression was unaffected by any of the stimuli. The effects of the stimuli were prevented by the antioxidant, α-lipoic acid, or the carbonyl scavenger, aminoguanidine.. The results provide evidence that oxidative stress is the common factor in the development of neuronal changes in diabetes; however, the mechanism by which oxidative stress occurs depends on the individual subpopulation of myenteric neurons examined. The presence of calbindin appears to protect myenteric neurons against harmful stimuli.

Topics: Animals; Calbindins; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Immunohistochemistry; Male; Myenteric Plexus; Neurons; Nitric Oxide Synthase Type I; Oxidative Stress; Rats; Rats, Wistar; S100 Calcium Binding Protein G; Vasoactive Intestinal Peptide

The pathogenetic mechanisms underlying gastrointestinal dysmotility in diabetic patients remain poorly understood, although enteric neuropathy, damage to interstitial cells of Cajal (ICC) and smooth muscle cell injury are believed to play a role. The aim of this study was to investigate the morphological and functional changes underlying intestinal dysmotility in RIP-I/hIFNβ transgenic mice treated with multiple very low doses of streptozotocin (20 mg/kg, i.p., 5 days). Compared with vehicle-treated mice, streptozotocin-treated animals developed type 1 diabetes mellitus, with sustained hyperglycaemia for 3.5 months, polyphagia, polydipsia and increased faecal output without changes in faecal water content (metabolic cages). Diabetic mice had a longer intestine, longer ileal villi and wider colonic crypts (conventional microscopy) and displayed faster gastric emptying and intestinal transit. Contractility studies showed selective impaired neurotransmission in the ileum and mid-colon of diabetic mice. Compared with controls, the ileal and colonic myenteric plexus of diabetic mice revealed ultrastructural features of neuronal degeneration and HuD immunohistochemistry on whole-mount preparations showed 15% reduction in neuronal numbers. However, no immunohistochemical changes in apoptosis-related markers were noted. Lower absolute numbers of neuronal nitric oxide synthase- and choline acetyltransferase-immunopositive neurons and enhanced vasoactive intestinal polypeptide and substance P immunopositivity were observed. Ultrastructural and immunohistochemical analyses did not reveal changes in the enteric glial or ICC networks. In conclusion, this model of diabetic enteropathy shows enhanced intestinal transit associated with intestinal remodelling, including neuroplastic changes, and overt myenteric neuropathy. Such abnormalities are likely to reflect neuroadaptive and neuropathological changes occurring in this diabetic model.

Topics: Animals; Choline O-Acetyltransferase; Colon; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Disease Models, Animal; Gastric Emptying; Gastrointestinal Motility; Ileum; Interferon-beta; Male; Mice; Mice, Transgenic; Myenteric Plexus; Nitric Oxide Synthase Type I; Receptor-Interacting Protein Serine-Threonine Kinases; Streptozocin; Substance P; Vasoactive Intestinal Peptide

The aim of this study was to investigate the ability of aminoguanidine (AG) to prevent diabetes-induced changes in nitric oxide synthase- (nNOS), vasoactive intestinal polypeptide- (VIP) and noradrenaline- (NA) containing nerves of the rat ileum using immunohistochemical and biochemical techniques. Diabetes was induced in adult male Wistar rats by a single intraperitoneal injection of streptozotocin (65 mg/kg). AG was administered in the drinking water to control (1.8 g/l) and diabetic (0.9 g/l) rats over a period of 8 weeks. Diabetes caused a significant increase in the thickness of nNOS-containing nerve fibres (p<0.001) in the circular muscle, in nNOS activity (p<0.05) and in the size distribution of nNOS-containing myenteric neurons (p<0.001). The thickness of VIP-containing nerve fibres was significantly greater (p<0.01) and there was a significant increase in varicosity size (p<0.01) and proportion of VIP-positive myenteric neurons (p<0.01) in diabetes. NA levels were significantly reduced (p<0.01) and the size of varicosities containing tyrosine hydroxylase (TH) was significantly increased (p<0.001) in diabetes. AG treatment completely or partially prevented the diabetes-induced increase in nNOS activity, in VIP-containing varicosity size, and in fibre width of both VIP- and nNOS-containing fibres in the circular muscle but had no effect on the diabetes-induced increase in nNOS-containing neuronal size or proportion of VIP-containing myenteric neurons. In contrast to VIP, AG treatment had no effect on the increase in TH-containing varicosity size in diabetes and also failed to prevent the decrease in NA levels induced by diabetes. These results indicate that AG treatment for neuropathy is not equally effective for all autonomic nerves supplying the ileum and that diabetes-induced changes in NA-containing nerves are particularly difficult to treat.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Enzyme Inhibitors; Guanidines; Ileum; Immunohistochemistry; Male; Myenteric Plexus; Nerve Degeneration; Neurons; Nitric Oxide Synthase Type I; Norepinephrine; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

Treatment with alpha-lipoic acid (LA) or evening primrose oil (EPO), individually, fails to prevent diabetes-induced changes in enteric nerves. Since synergy between these treatments has been reported, the aim was to investigate the effectiveness of combined LA/EPO treatment. LA and EPO were administered in the diet (approximately 80 and 200 mg/kg/day, respectively) to control and diabetic (induced by streptozotocin, 65 mg/kg, i.p.) rats. For prevention, treatment started after 1 week and lasted 7 weeks. For reversal, treatment lasted 4 weeks and was initiated after 8 weeks. Nerves supplying the ileum containing vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and noradrenaline (NA) were examined immunohistochemically or biochemically. Diabetes caused a significant increase in VIP-containing cell bodies (p<0.001), decrease in NA content (p<0.01) and loss of CGRP-immunoreactivity. LA/EPO treatment totally prevented diabetes-induced changes in VIP (p<0.001) and CGRP and partially reversed (p<0.05) these changes once they had been allowed to develop. In contrast, treatment had no effect on diabetes-induced changes in NA-containing nerves. Therefore, LA and EPO are only effective at treating diabetes-induced changes in some enteric nerves when administered in combination. However, diabetes-induced changes in NA-containing nerves are resistant to treatment.

Topics: Animals; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Synergism; Drug Therapy, Combination; Fatty Acids, Essential; gamma-Linolenic Acid; Ileum; Immunohistochemistry; Linoleic Acids; Male; Myenteric Plexus; Neuroprotective Agents; Norepinephrine; Oenothera biennis; Plant Oils; Rats; Rats, Wistar; Thioctic Acid; Vasoactive Intestinal Peptide

The aim of the study was to investigate antioxidant (alpha-lipoic acid [LA]) and gamma-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 gamma-linolenic acid (present in evening primrose oil [EPO]) were administered as dietary supplements ( approximately 80 and 200 mg. kg(-1). 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.

Topics: Animals; Antioxidants; Autonomic Nervous System Diseases; Autonomic Pathways; Calcitonin Gene-Related Peptide; Diabetic Neuropathies; gamma-Linolenic Acid; Heart Conduction System; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Norepinephrine; Penis; Rats; Rats, Wistar; Thioctic Acid; Vasoactive Intestinal Peptide

The effect of the treatment with acetyl-L-carnitine (ALC) on neurons releasing the vasoactive intestinal polypeptide (VIP) of the submucous plexus in the jejunum of diabetic rats was the purpose of our investigation. Diabetes (DM) was induced by injecting streptozotocin endoveneously (35 mg/kg). After sacrificing the animals, the jejunum was collected and processed for VIP detection. Four groups were used: C (non-diabetic), CC (non-diabetic treated with ALC), D (diabetic), DC (diabetes treated with ALC). We analyzed the immunoreactivity and the cellular profile of 126 cell bodies. The treatment with ALC improved some aspects of DM. However, it promoted a small increase in the area of neurons from group CC, suggesting a possible neurotrophic effect. Neurons from groups D and DC showed a large increase in their cellular profile and immunoreactivity when compared to C and CC, suggesting a larger concentration of this neurotransmitter within the neurons that produce it. This observation constitutes a recurrent finding in diabetic animals, suggesting that ALC does not interfere in the pathophysiological mechanisms that unchain a higher production and/or neurotransmitter accumulation and increase the profile of the VIP-ergic neurons.

Topics: Acetylcarnitine; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dietary Supplements; Immunohistochemistry; Jejunum; Male; Neurons; Nootropic Agents; Rats; Rats, Wistar; Streptozocin; Submucous Plexus; Vasoactive Intestinal Peptide

Neuropeptide Y is a regulatory peptide found in adrenergic and non-adrenergic neurons. Diabetes, which may cause autonomic neuropathy, induces an increase in hypothalamic neuropeptide Y (NPY) levels; thereby we measured the effects of chronic diabetes on neuropeptide Y in the intestine. Rats were injected with streptozotocin (65 mg/kg) and maintained for up to 20 weeks. Another group of rats was injected with 6-hydroxydopamine (50 mg/kg) x 2 to induce sympathectomy. Ileum and colon were harvested and both whole and microdissected intestine were (1) stained with antibodies to neuropeptide Y, vasoactive intestine polypeptide, and neurofilaments or (2) extracted for neuropeptide Y radioimmunoassay. Neuropeptide Y levels were similar under all conditions in the colon, but there was a trend toward an increase in the diabetic whole ileum. NPY levels were significantly increased in the dissected myenteric plexus ileal layer in diabetics. We noted an increase in the number of neuropeptide Y and vasoactive intestine polypeptide immunoreactive myenteric neurons in diabetics and after 6-hydroxydopamine-induced sympathectomy. Diabetes, and to a lesser extent sympathectomy, induced an increase in ileal neuropeptide Y levels and neuropeptide Y-staining myenteric but not submucosal neurons. Altered tissue levels of neuropeptide Y may account for certain of the gastrointestinal disturbances commonly seen in diabetes.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Immunohistochemistry; Intestinal Mucosa; Intestines; Myenteric Plexus; Neurofilament Proteins; Neurons; Neuropeptide Y; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Staining and Labeling; Vasoactive Intestinal Peptide

The effect of acrylamide intoxication (a widely used model for autonomic neuropathy) on the fluorescence intensity and density of catecholamine- and peptide-containing nerve fibres and tissue content of noradrenaline and the peptides vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P and neuropeptide Y in the enteric nerves of rat ileum was examined. Histochemical and immunohistochemical techniques were used to localize catecholamine- and peptide-containing nerve fibres. The tissue content of noradrenaline was measured using high-performance liquid chromatography, and an enzyme-linked immunosorbent assay technique was used to determine the tissue content of the peptides investigated. Acrylamide intoxication caused a significant decrease in the density of catecholamine-containing nerve fibres and tissue content of noradrenaline in the myenteric plexus of rat ileum. A decrease in tissue content and immunoreactivity of calcitonin gene-related peptide and an increase in vasoactive intestinal polypeptide was seen in the myenteric plexus of ileum from acrylamide-intoxicated rats. In the submucous plexus, the acrylamide treatment caused a decrease in calcitonin gene-related peptide immunoreactivity and an increase in vasoactive intestinal polypeptide and neuropeptide Y immunoreactivity. There was no change in either tissue content or immunoreactivity of substance P in both myenteric and submucous plexuses of the treated rat ileum. These changes have a striking similarity with those found in the enteric nerves of streptozotocin-diabetic rat ileum, suggesting the possible presence of an underlying common mechanism(s) in the development of neuropathic changes in the autonomic nerves of acrylamide-intoxicated and streptozotocin-diabetic rats.

Topics: Acrylamide; Acrylamides; Animals; Autonomic Pathways; Calcitonin Gene-Related Peptide; Catecholamines; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Intestines; Male; Nerve Fibers; Neuropeptide Y; Norepinephrine; Rats; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide

To determine the effect of diabetes mellitus on the levels of substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP) in the rat cornea and iris.. Corneas and irides from control and diabetic rats were processed for neuropeptide radioimmunoassay 3 months after induction of diabetes with streptozotocin. Corneas and irides also were processed for SP and CGRP immunohistochemistry and were evaluated qualitatively.. The radioimmunoassay data revealed no significant differences in either the content or concentration of SP, CGRP, and VIP between control and diabetic corneas. In contrast, iridial levels of CGRP and SP were significantly increased by 38% and 256%, respectively, in the diabetic animals. Iridial VIP levels were unchanged in the diabetic versus control groups. Immunohistochemical demonstrations of corneal and iridial SP- and CGRP-immunoreactive fiber plexuses were indistinguishable on the basis of purely qualitative criteria.. The results of this study have demonstrated a target- and peptide-specific effect of short-term diabetes on SP and CGRP expression in ocular nerves of the anterior eye segment. The absence of demonstrable changes in corneal neuropeptide levels argue against the theory that corneal abnormalities seen in clinical diabetes are caused, in part, by deficits in synthesis or axonal transport of "trophic" peptides in corneal sensory nerves. In contrast, elevated iridial SP and CGRP levels may be responsible for reported clinical deficits in pupillary diameter regulation.

Topics: Animals; Calcitonin Gene-Related Peptide; Cornea; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Female; Immunoenzyme Techniques; Iris; Neurons; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Substance P; Vasoactive Intestinal Peptide

Complications of diabetes include sensory and autonomic neuropathy. The aim of the present paper was to study the degree of sensory and autonomic neuropathy and correlate these findings with the distribution and density of neuropeptidergic nerve fibers in the skin of the forearm of diabetic patients and healthy controls. We investigated 30 diabetics (24 type 1 and 6 type 2) and compared them with 13 healthy controls. There were no differences between the groups with respect to density and distribution of nerve fibers displaying immunoreactivity to the pan-neuronal marker PGP 9.5 and sensory and parasympathetic neuropeptides (substance P, calcitonin gene-related peptide and vasoactive intestinal peptide). By contrast, nerve fibers containing neuropeptide Y, a marker of sympathetic neurons, were reduced in number in the diabetic patients. C-fiber function (measured as the axon-reflex-evoked flare response) became impaired with increasing age in all subjects. The diabetic patients, however, showed a reduced flare compared to age-matched healthy controls. The reduction was particularly prominent in the younger patients (20-50 years). There was a greater reduction of the flare in neuropathic patients than in non-neuropathic patients, but there was no correlation between the degree of functional impairment and the duration of the disease.

Topics: Adult; Aged; Autonomic Nervous System; Axons; Calcitonin Gene-Related Peptide; Case-Control Studies; Diabetes Mellitus; Diabetic Neuropathies; Female; Forearm; Humans; Male; Middle Aged; Nerve Fibers; Neurons, Afferent; Neuropeptide Y; Parasympathetic Nervous System; Skin; Substance P; Sympathetic Nervous System; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactivity are reduced in the cutaneous nerves of diabetic patients with peripheral neuropathy. The functional significance of this finding was studied by measuring the forearm sweat response to intradermal methacholine and the effect of coadministration of VIP and SP in six normal subjects, and in six diabetic patients with neuropathy and eight without. Flare responses to the two peptides were also measured. Methacholine-induced sweat output was significantly greater in neuropathic patients compared with the other groups (p < 0.05), suggesting upper limb denervation supersensitivity. VIP and SP alone did not evoke sweating in any subject. Injection of VIP or SP reduced methacholine-induced sweating to a similar degree in all groups, except that the reduction was smaller in the non-neuropathic group than in the others (p = 0.028 versus normal subjects, p = 0.014 versus neuropathic diabetic patients). Flare responses to the peptides were markedly reduced in the neuropathic patients compared with the other groups (p < 0.01). In neuropathic patients, increased sweat responses and decreased flare coexist with diminished neurophysiological measurements; cutaneous sweating and flare responses provide valuable additional information to conventional methods of neurological assessment in diabetic neuropathy.

Topics: Adult; Blood Vessels; Diabetic Neuropathies; Humans; Male; Methacholine Chloride; Middle Aged; Peripheral Nervous System Diseases; Substance P; Sweating; Vasoactive Intestinal Peptide

Basal and postprandial levels of gastrin, somatostatin, vasoactive intestinal polypeptide (VIP) and pancreatic polypeptide (PP) were followed up in 105 patients with non insulin dependent diabetes mellitus (20 with autonomic neuropathy only, 35 with peripheric neuropathy only, 30 with autonomic and peripheric neuropathy simultaneously and 20 without any sign of neuropathy) and in the control group of 40 individuals. Serum levels of gastrin, somatostatin, VIP and PP are determined by a RIA (used kits of Prof. SR Bloom, Hammersmith Hospital, London). The results of investigation showed significantly higher basal and postprandial levels of gastrin and VIP in patients with autonomic neuropathy in comparison with the group without neuropathy and with the control group (p < 0.001). The serum levels of somatostatin did not differ significantly between the groups of diabetics with and without neuropathy. Basal level of PP was significantly lower and postprandial PP levels remained low in patients with autonomic neuropathy in comparison with the group without neuropathy (p < 0.001). We postulate that basal and postprandial gastrin and VIP levels raised secondary to partial vagotomy in diabetics with autonomic neuropathy. Measuring PP serum levels in diabetics after a protein rich meal can be useful to check vagus nerve function in the gastrointestinal tract in order to detect autonomic neuropathy.

Topics: Adult; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Gastrins; Gastrointestinal Hormones; Humans; Male; Middle Aged; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide

The effect of diabetes on the density of peptide-containing nerves in the pyloric sphincter of streptozotocin-induced diabetic rats and the possible preventive action of the ganglioside mixture AGF1 on the diabetes-induced changes were investigated.. Immunohistochemical techniques were used to localize the general neuronal marker protein gene product 9.5 and the neuropeptides, calcitonin gene-related peptide, [met]-enkephalin, neuropeptide Y, substance P, and vasoactive intestinal polypeptide.. The density of neurones showing immunoreactivity to the above peptides in nerves supplying the thickened circular muscle layer of the pyloric sphincter was reduced extensively in diabetic rats. In the ganglioside-treated diabetic animals, this reduction was prevented; indeed, calcitonin gene-related peptide- and substance P-like immunoreactivity in the ganglioside-treated diabetic rats exceeded that seen in control animals. In the ganglioside-treated controls, there was no significant difference in the peptide immunoreactivity from that of untreated controls.. The results of the present study show that the ganglioside mixture AGF1 is effective in protecting the nerves of the pyloric sphincter from diabetes-induced changes.

Topics: Animals; Biomarkers; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Enkephalin, Methionine; Fluorescent Antibody Technique; Gangliosides; Male; Neurons; Neuropeptide Y; Pylorus; Rats; Rats, Wistar; Substance P; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan-neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18-46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n = 6), with diabetes for 6 months to 3 years; group 2 (n = 5), with the disease for 5-10 years; and group 3 (n = 7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P < 0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P < 0.05). Twenty-eight per cent (5/18) of all patients showed high VIP-IR around sweat glands (> 95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (< 5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P = 0.002), presence of clinical autonomic neuropathy (Fisher exact test P = 0.04), and a reduced sural nerve conduction velocity (Fisher exact test P = 0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests.

Topics: Adolescent; Adult; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Immunohistochemistry; Male; Middle Aged; Skin; Sweat Glands; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Some neurochemical changes in the gut of rats after five weeks of alloxan-induced diabetes were investigated. It was found that at this stage of diabetes the changes were restricted mainly to the small intestine with a special selectivity for the duodenum. No changes were found in the most part of the large intestine and rectum. The methionine-enkephalin content was markedly reduced throughout the small intestine, while vasoactive intestinal polypeptide was increased in duodenum, ileum and caecum. Substance P content was unaffected, while at later stages of the disease it was significantly reduced in the entire small intestine. Sympathetic noradrenaline and intrinsic serotonin contents were significantly increased in the duodenum and unchanged throughout the rest of the intestine. These data suggest that the small intestine and caecum might be the early target of diabetic autonomic neuropathy, that might involve progressively the rest of the large intestine at later stages as recent results have suggested. It is likely that the gastrointestinal dysfunctions, often present in diabetic patients, might also be due to the combined pre-synaptic alterations, and to the functional imbalance between Gs and Gi/Go transduction proteins recently reported. Insulin therapy, begun seven days after alloxan treatment, reduced drastically the hyperglycaemia, restored normal body growth and prevented all the gut neurochemical changes associated with alloxan-induced diabetes.

Topics: Animals; Autonomic Nervous System Diseases; Diabetes Mellitus, Experimental; Diabetic Neuropathies; GTP-Binding Proteins; Intestinal Mucosa; Intestines; Male; Neuropeptides; Rats; Rats, Sprague-Dawley; Serotonin; Signal Transduction; Substance P; Vasoactive Intestinal Peptide

Autonomic neuropathy and gastrointestinal problems are among the most common complications of diabetes. In this report it is shown that a possible correlation between the two disorders might exist, since diabetes causes a profound alteration of the peptidergic innervation of the gut. It is reported that 14 weeks after diabetes induction with alloxan the levels of substance P and methionine-enkephalin are markedly reduced throughout the intestine, while vasoactive intestinal polypeptide content is dramatically increased. Therefore the enteric innervation of diabetic animals is completely disorganized, with some systems undergoing atrophy and others undergoing hypertrophy. Treatment of diabetic animals with acetyl-L-carnitine prevents the onset of the marked peptide changes described above. The results suggest a potential for acetyl-L-carnitine in the treatment of autonomic neuropathies.

Topics: Acetylcarnitine; Animals; Autonomic Nervous System Diseases; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Enkephalin, Methionine; Intestinal Mucosa; Intestines; Male; Neuropeptides; Rats; Rats, Sprague-Dawley; Substance P; Vasoactive Intestinal Peptide

Image-analysis was used to measure nerves immunoreactive to the general neuronal marker protein gene product 9.5 (PGP 9.5-IR) and the neuropeptides calcitonin gene-related peptide and vasoactive intestinal polypeptide in standardised leg skin biopsies of three age-matched groups of young subjects: non-diabetic (n = 14), diabetic patients with normal small fibre function ("non-neuropathic", (n = 11) and diabetic patients with abnormal small fibre function ("neuropathic", n = 11). Depletion of nerves and neuropeptides was most marked in the epidermis, where calcitonin gene-related peptide-immunoreactivity was more frequently absent than PGP 9.5-IR in diabetic patients. Epidermal PGP 9.5-IR nerve area and counts were reduced in neuropathic compared with normal subjects (p less than 0.001), as were epidermal calcitonin gene-related peptide nerve counts (p = 0.003). Sweat gland PGP 9.5 and vasoactive intestinal polypeptide, which may be involved in sweat production, showed no diminution in diabetic patients (area: p = 0.160, p = 0.372 by ANOVA). Two diabetic patients showed elevated sweat gland PGP 9.5-IR and three had increased sweat gland vasoactive intestinal polypeptide; this may represent nerve proliferation. In local sweat tests, acetylcholine-stimulated sweat output was associated with increased immunoreactivity, while the sympathetic skin response showed inverse correlations with immunoreactivity. There were no consistent changes with other commonly-used neurophysiological tests. HbA1 correlated negatively with immunohistochemical measurements. Neuropeptide changes were seen in the absence of macro- and microvascular disease, and epidermal nerve depletion occurred in patients with normal thermal thresholds and cardiac autonomic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Analysis of Variance; Calcitonin Gene-Related Peptide; Diabetic Neuropathies; Female; Fluorescent Antibody Technique; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neuropeptides; Skin; Sweat Glands; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

The concentration of vasoactive intestinal polypeptide (VIP) was measured in cerebrospinal fluid (CSF) obtained from diabetic patients with neuropathy and their age-matched control subjects. VIP level in CSF from diabetic patients was significantly decreased as compared with that from the controls (12.9 +/- 3.1 pg/ml vs. 35.4 +/- 3.3 pg/ml, p less than 0.01). Decreased VIP level in CSF may relate with diabetic neuropathy in particular sexual dysfunction.

Topics: Adult; Diabetic Neuropathies; Humans; Hypogonadism; Male; Middle Aged; Radioimmunoassay; Vasoactive Intestinal Peptide

We have previously shown depletion of nerves and neuropeptides in skin biopsies of diabetic patients, even in the absence of clinical signs and symptoms of sensory and autonomic neuropathy, but were unable to examine the changes occurring at an early stage of the disease. Therefore, the distribution and relative density of peptide-containing nerves was studied in streptozotocin-treated rats in order to assess the progression of neural changes in the initial stages of diabetes. Skin samples dissected from the lip and footpad of diabetic rats, 2, 4, 8 and 12 weeks after streptozotocin injection and age matched controls were sectioned and were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), and to a general neural marker, protein gene product 9.5 (PGP 9.5). No change was apparent in the distribution or relative density of immunoreactive cutaneous nerve fibres 2, 4 and 8 weeks after streptozotocin treatment. By 12 weeks there was a marked increase in the number of CGRP-immunoreactive fibres present in epidermis and dermis, and of VIP-immunoreactive fibres around sweat glands and blood vessels. A parallel increase was seen in nerves displaying PGP 9.5 immunoreactivity. No differences were detected in nerves immunoreactive for either substance P in the epidermis and dermis, and NPY around blood vessels. The alterations in the peptide immunoreactivities may be similar in the initial stages of human diabetes.

Topics: Animals; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Fluorescent Antibody Technique; Male; Nerve Fibers; Neuropeptide Y; Neuropeptides; Rats; Rats, Inbred Strains; Skin; Substance P; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

After induction of diabetes with streptozocin (STZ-D) in rats, we measured vasoactive intestinal polypeptide (VIP) content in sciatic nerve and spinal cord obtained from nondiabetic, untreated STZ-D, and insulin-treated STZ-D rats. Eight weeks after the onset of diabetes, caudal nerve conduction velocity (NCV) in the untreated STZ-D rats (n = 13) was slower than in the controls (n = 11; mean +/- SE 30.9 +/- 0.6 vs. 41.4 +/- 1.8 m/s, P less than 0.001). The decrease in NCV was less marked in the insulin-treated STZ-D rats (n = 11; 36.3 +/- 0.9 m/s, P less than 0.05 vs. control). VIP content in sciatic nerve decreased in the untreated STZ-D rats (1.33 +/- 0.23 ng/g wet wt) compared with the other groups (control, 3.10 +/- 0.44, P less than 0.01; insulin-treated STZ-D, 2.44 +/- 0.55, P less than 0.05). However, in spinal cord, VIP content was not significantly different among the three groups. The VIP levels in sciatic nerve showed a positive correlation with NCV (r = 0.430, P less than 0.01). In addition, an inverse correlation between VIP levels and blood glucose levels was observed (r = -0.5624, P less than 0.001). NCV was also inversely correlated with blood glucose levels (r = -0.7662, P less than 0.001). Together with a previous morphological study, these findings suggest a possible causal relationship between reduced VIP content and diabetic neuropathy.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Insulin; Male; Neural Conduction; Radioimmunoassay; Rats; Rats, Inbred Strains; Sciatic Nerve; Spinal Cord; Vasoactive Intestinal Peptide

Immunocytochemistry for the general neuronal marker protein gene product 9.5 and four neuropeptides (calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide and neuropeptide Y) was performed on 20 skin biopsy specimens from 19 diabetic patients, age range 20-75 years, 17 Type 2 (non-insulin-dependent) and 3 Type 1 (insulin-dependent). Fifteen specimens were from the lower limb, 3 from the upper limb and 2 from the abdominal wall. Seven subjects had lower limb neurophysiological tests. All but one specimen showed reduced protein gene product 9.5 and neuropeptide immunoreactivity. Reduced protein gene product 9.5 and neuropeptide immunoreactivity was found in specimens taken from the abdominal wall and hand as well as those from the leg, and also in specimens from patients undergoing amputation for peripheral vascular disease. In general, the greater the number of abnormal neurophysiological tests, the greater the extent of neuronal abnormalities. Three patients with normal tests had abnormalities of dermal innervation. While these changes are also found in other axonal neuropathies, in the absence of other causes of peripheral nerve disease and of macrovascular disease, immunocytochemistry of skin biopsies may have a role in the assessment of diabetic neuropathy and its response to treatment.

Topics: Adult; Aged; Biopsy; Calcitonin Gene-Related Peptide; Diabetes Mellitus; Diabetic Neuropathies; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Skin; Substance P; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

The monoaminergic innervation of the central nervous system (CNS) is characterized by long and short projecting neurons. The neurological correlates of diabetes are usually referred to as processes of degenerative atrophy affecting motor and sensory peripheral nerves. We have found that the long serotoninergic axons innervating the spinal cord and the cerebral cortex are unaffected in diabetic animals and that the noradrenergic innervation of the cortex is normal as well. The serotonin content is doubled in the hypothalamus with no apparent alteration of 5-HIAA levels, suggesting a supernumerary innervation that is accompanied by a reduced release. In pons medulla oblongata, serotonin and dopamine with the relative metabolites 5-HIAA and DOPAC are significantly reduced, whereas noradrenaline is markedly increased. In the hippocampus, there is a reduction of serotonin content. The serotoninergic alterations are peculiar as suggested by the sparing of the most distal projections that is accompanied by hyperinnervation of the hypothalamus and the loss of shorter collaterals in the pons medulla oblongata. In the hypothalamus and in the striatum of diabetic rats, there are significant higher levels of substance P and met-enkephalin, respectively. The abundance of proenkephalin A mRNA is also increased in the striatum. Conversely, in the lumbar cord of diabetic animals, the levels of substance P and met-enkephalin are significantly reduced. Such alterations likely reflect retrograde degeneration of the peripheral sensory input. The CNS changes are unlikely due to vascular abnormalities in the brain of diabetic rats; rather, we suggest that the persistent lack of insulin is the major factor involved as a trigger of the monoaminergic changes in the diabetic brain.

Topics: Animals; Biogenic Monoamines; Brain; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Enkephalin, Methionine; Male; Neuropeptides; Rats; Rats, Inbred Strains; Substance P; Vasoactive Intestinal Peptide

The distribution of adrenergic and vasoactive intestinal polypeptide-, neuropeptide Y- and substance P-immunoreactive nerves was studied histochemically and immunohistochemically in the irides of rats 8 weeks after the induction of diabetes with streptozotocin. In the control animals, catecholamine-containing, vasoactive intestinal polypeptide- and substance P-immunoreactive nerve fibres were found in the constrictor pupillae, dilator muscle and the ciliary processes. They also formed perivascular nerve plexuses of blood vessels in the dilator muscle. Neuropeptide Y-immunoreactive nerve fibres were only observed in the dilator muscle and ciliary processes. In the irides from diabetic animals, a considerable increase was observed in the fluorescence intensity and/or density of vasoactive intestinal polypeptide-immunoreactive nerves. Some varicosities of the vasoactive intestinal polypeptide-immunoreactive nerves appeared enlarged. In contrast, no apparent change in the density and/or fluorescence intensity of catecholamine-containing, neuropeptide Y- and substance P-immunoreactive nerve fibres was observed in the irides from diabetic animals when compared with controls. The results are discussed in relation to the symptoms of autonomic neuropathy of the irides in diabetes.

Topics: Adrenergic Fibers; Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Iris; Male; Nerve Fibers; Neuropeptide Y; Rats; Rats, Inbred Strains; Substance P; Vasoactive Intestinal Peptide

1. Immunohistochemical, immunoblotting and release experiments were performed on ileum from control rats, from 8-week streptozotocin-diabetic rats and from diabetic rats after acute application of insulin in vitro. 2. There was an increase in vasoactive-intestinal-polypeptide-like and a decrease in calcitonin-gene-related-peptide-like immunoreactivity in the myenteric plexus of the diabetic rat ileum, although electrically evoked release of both peptides from enteric nerves was defective. Acute application of insulin in vitro reversed the defective release and changes in immunoreactivity of vasoactive intestinal polypeptide and calcitonin-gene-related peptide seen in the enteric nerves of streptozotocin-diabetic rat ileum. 3. In addition, using a monoclonal neurofilament antibody RT 97 that recognizes a phosphorylated neurofilament epitope present in normal enteric nerves, it was shown that this phosphorylated neurofilament epitope was absent in diabetic nerves, even though a polyclonal neurofilament antibody revealed that neurofilaments were present in both axons and cell bodies of the myenteric plexus of diabetic rat ileum. After only 2 h of insulin incubation in vitro, the phosphorylated neurofilament epitope was again present in the nerves. 4. It is suggested that the abnormal distribution of phosphorylated neurofilaments and defective storage and release of vasoactive intestinal polypeptide and calcitonin-gene-related peptide in the present study may be a more general feature of diabetes. The restoration of these abnormalities by continuous acute insulin application in vitro shown here suggests that the availability of a steady level of insulin might prevent some of the changes which occur in early stages of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Ileum; In Vitro Techniques; Insulin; Intermediate Filaments; Male; Myenteric Plexus; Neuropeptides; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

Lack of release of vasoactive intestinal polypeptide and calcitonin gene-related peptide during electrical stimulation of enteric nerves in streptozotocin-diabetic rats.

Topics: Animals; Calcitonin Gene-Related Peptide; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Ileum; Intestines; Neuropeptides; Peripheral Nerves; Rats; Vasoactive Intestinal Peptide

Penile tissue (consisting of corpus cavernosum and tunica albuginea) was obtained from 19 patients undergoing surgery for the implantation of penile prostheses. The tissue was examined for vasoactive intestinal polypeptide-like immunoreactivity in nerves, acetylcholinesterase-positive staining in nerves and noradrenaline content. Impotence was due to a variety of causes; 11 patients were classified as a 'non-neuropathic' group on the basis of their clinical history which included Peyronie's disease, vascular disease, hypertension and psychogenic impotence. Vasoactive intestinal polypeptide-like immunoreactive and acetylcholinesterase-positive nerves were present and the pattern and distribution were similar in each patient in this group. The noradrenaline content of the tunica albuginea was significantly lower than the corpus cavernosum (p less than 0.02), although there was a linear relationship between the noradrenaline contents of the two regions (r = 0.95, p less than 0.01). By comparison, a complete absence of vasoactive intestinal polypeptide-like immunoreactivity in nerves was observed in a patient with a cauda equina lesion. Five out of six diabetic patients studied revealed a marked reduction in vasoactive intestinal polypeptide-like immunoreactivity in nerves associated with the cavernous smooth muscle, while acetylcholinesterase-positive staining was reduced in three out of five diabetic patients studied. The noradrenaline content of the corpus cavernosum from diabetic patients was significantly lower (p less than 0.02) than that of the 'non-neuropathic' group. The noradrenaline content of the tunica albuginea, however, was similar in both groups. The results provide evidence that VIPergic, cholinergic and adrenergic nerves in the penis are affected in diabetes mellitus and thus may contribute to the development of impotence in diabetic patients.

Topics: Acetylcholinesterase; Aged; Diabetes Complications; Diabetic Neuropathies; Erectile Dysfunction; Humans; Male; Middle Aged; Norepinephrine; Parasympathetic Nervous System; Penis; Staining and Labeling; Sympathetic Nervous System; Vasoactive Intestinal Peptide

The autonomic innervation of the seminal vesicle from 8 and 16 week streptozotocin-induced diabetic rats and age-matched controls was studied by pharmacological, histochemical and immunohistochemical methods. Contractions in response to electrical field stimulation, which were abolished using prazosin (2 microM) or tetrodotoxin (one to 1.6 microM), and to noradrenaline were significantly increased in both eight and 16 week diabetic animals. The contractile response to acetylcholine was significantly increased in the 16 week diabetic rats only, when compared with controls. Although these responses were significantly increased, no difference was found in ED50 and EF50 values between control and diabetic rats. Vasoactive intestinal polypeptide (0.3 microM) had no effect on resting tension or nerve-mediated responses. In seminal vesicles from control animals, both vasoactive intestinal polypeptide-immunoreactive and acetylcholinesterase-containing nerves were localised around the folds of the columnar epithelium of secretory cells, in contrast to neuropeptide Y-immunoreactive and catecholamine-containing nerves which were found in the smooth muscle layers. In seminal vesicles from both eight and 16 week diabetic animals no difference was seen in distribution or density of acetylcholinesterase-containing nerves; there was an increase in density and fluorescence intensity of vasoactive intestinal polypeptide- and neuropeptide Y-immunoreactive nerves and a decrease in catecholamine-containing nerves compared with controls. The results are discussed in relation to autonomic neuropathy in diabetes.

Topics: Acetylcholine; Adrenergic Fibers; Animals; Cholinergic Fibers; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dose-Response Relationship, Drug; Electric Stimulation; Histocytochemistry; Immunohistochemistry; Male; Neuropeptide Y; Norepinephrine; Peptides; Prazosin; Rats; Seminal Vesicles; Tetrodotoxin; Time Factors; Vasoactive Intestinal Peptide

Enteric nerves in the ileum of rats 8 weeks after streptozotocin-induction of diabetes were examined under the electron microscope before and after immunolabeling for vasoactive intestinal polypeptide (VIP). These studies have provided evidence of degenerative changes in the myenteric nerve fibres of diabetic rats, many of which were shown to contain VIP. It is suggested that VIP-ergic nerves in the gut may play a role in the development of gastrointestinal dysfunction in diabetes.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Ileum; Male; Microscopy, Electron; Myenteric Plexus; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide