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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylcholine (ACh), choline acetyltransferases and cholinesterases occur in cornea, iris-ciliary body complex and retina of several vertebrates. In cornea, ACh may serve as a sensory transmitter as well as a local hormone, the function of which is not delineated. The function of ACh as the parasympathetic neurotransmitter at the iris and ciliary body is well established. The muscarinic receptors on the iris smooth muscle are similar to the muscarinic receptors (M2 type in two way classification) at other smooth muscles towards their interaction with agonists and antagonists. Binding studies using radiolabeled antagonists and their displacement by agonists indicate that muscarinic receptors in membranes of iris-ciliary body complex are heterogeneous indicating more than one subtype of muscarinic receptors. A subtype other than M2 receptors may occur at the presynaptic sites of parasympathetic nerves, which have yet to be investigated using specific agonists and antagonists. Cholinergic markers, choline acetyltransferase and acetylcholinesterase, differ quantitatively and qualitatively in retinas of different species. However, amacrine cells are cholinergic in all vertebrate species. Although they make up 1% of retinal neurons, they influence the activity of a majority of ganglion cells. Cholinergic effects in ganglia are mediated through nicotinic and muscarinic receptors. Both of these types of cholinergic receptors are heterogeneous. They have yet to be investigated for their subtypes using specific agonists and antagonists. Although the role of cholinergic retinal neurons in the processing of visual information is not known, their input to ganglion cells generally increases the rate of spontaneous activity or the number of action potentials in light-evoked responses. Thus, the cholinergic input seems to modify the overall neuronal input to the ganglion cells from the receptive fields. Endothelial cells of blood vessels contain muscarinic receptors, which are activated by ACh to cause relaxation. Although retinal blood vessels provide recognizable characteristic signs in diabetes mellitus and hypertensive disease, no information is available on the muscarinic receptors of these vessels.
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PMID:Cholinergic systems and multiple cholinergic receptors in ocular tissues. 391 49

We measured the content of the two principal neurotransmitters of the autonomic nervous system from the erectile tissue of four men with normal erection and 38 men impotent as a result of injury or disease. In the former the norepinephrine content was 812 +/- 82.6 (SE) pg per mg of wet weight; In the latter, statistically significant reductions of norepinephrine were found with the greatest decrease occurring with insulin-dependent diabetes mellitus. Neither choline acetyltransferase activity nor morphologic alterations of the nerve fibers of erectile tissue were observed in either group. Our findings suggest that the sympathetic nervous system is an integral component of human erection and that a functional alteration of the corporal nerve fibers occurs with several diseases associated with impotence.
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PMID:Alteration of the penile corpora in patients with erectile impotence. 610 68

This investigation was designed to determine whether the aldose reductase inhibitor Sorbinil prevented the development of or reversed defects of nerve conduction and axonal transport in streptozotocin-diabetic rats. Untreated diabetes of either 3 or 6 wk duration caused a fall in sciatic motor nerve conduction velocity (MNCV) of 6-9 m/s (P less than 0.001) and significantly reduced the accumulation of axonally transported choline acetyltransferase activity against a 24-h sciatic nerve crush. These functional defects were associated with accumulation of sorbitol and depletion of myo-inositol in the sciatic nerve. Treatment with Sorbinil (25 mg/kg/day, p.o.) throughout the period of diabetes prevented the development of all these abnormalities in both 3- and 6-wk diabetic groups. In a second study, three groups of rats were subject to 3 wk untreated diabetes followed by Sorbinil treatment (as above) for 1, 2, or 3 wk to determine whether the abnormalities expected from 3 wk of untreated diabetes could be reversed. One week of treatment significantly elevated both MNCV and choline acetyltransferase accumulation (P less than 0.05). The longer treatments progressively ameliorated these defects such that the group that received Sorbinil for the second 3 wk of a 6-wk diabetic period gave values that were similar to controls and to diabetic rats that had been given Sorbinil throughout their diabetes. Sorbitol accumulation was markedly reduced by only 1 wk of Sorbinil treatment, but the normalization of myo-inositol levels required 2 wk of treatment. These findings indicate that Sorbinil treatment in diabetic rats prevented and reversed both Sorbitol accumulation and depletion of nerve myo-inositol in the sciatic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 May
PMID:Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor Sorbinil. 620 76

The adrenergic and cholinergic innervation of the bladder was studied in streptozotocin-diabetic rats. The presence of hypertrophy and distension in the 'diabetic' bladders necessitates care in assessing changes occurring in the nerves, factors which are also relevant to clinical histochemical studies. Biochemical assays of cholinergic enzymes revealed decreased activities per g wet weight tissue. However, the total activities of choline acetyltransferase and acetylcholinesterase per whole bladder were significantly increased after 2 weeks of diabetes with greater changes by 8 weeks. Total dopamine levels per bladder were significantly higher than in control rats in the 2-week but not the 8-week group of animals; this may indicate an initial increase in adrenergic nerve activity. There was no impairment in the ability of the detrusor muscle to respond to noradrenaline, acetylcholine or to cholinergic nerve stimulation. Shortly after induction of diabetes streptozotocin-treated rats display polyuria. It is proposed that the activity of the bladder is therefore stimulated to allow greater volumes of urine to be passed. The results are discussed in relation to human diabetes mellitus where clinical studies have implicated a neuropathic origin to bladder dysfunction.
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PMID:Rat bladder in the early stages of streptozotocin-induced diabetes: adrenergic and cholinergic innervation. 623 Dec 6

The regular occurrence of autonomic neuropathy, colonic dilatation, and loss of fecal consistency was investigated in streptozotocin-diabetic, age-matched control, and pancreatic-islet--transplanted rats using ultrastructural, histochemical, and biochemical methods. Degenerating unmyelinated axons were observed by electron microscopy in the colonic submucosa and muscularis, ileal mesentery, and splenic pedicle in 5--7 months diabetic animals; similar changes were not found in control rats or animals subjected to islet transplantation three weeks after induction of diabetes and sacrificed 4--6 months later (colon only). Regenerative changes, including axons with identifiable growth cones, were demonstrated in the mesenteric nerves of chronically diabetic animals. Formaldehyde-induced catecholamine fluorescence and cholinesterase histochemistry suggested deficiencies in colonic adrenergic and cholinergic innervation; histochemical findings in islet-transplanted animals were comparable to those of untreated control animals. Biochemical measurements of the adrenergic and cholinergic nervous system marker enzymes dopamine-beta-hydroxylase and choline acetyltransferase, respectively, in colon and spleen confirm a deficit in adrenergic (colon and spleen) and cholinergic (colon) innervation in chronically diabetic animals.
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PMID:Experimental diabetic autonomic neuropathy. 645 33

Adrenergic, cholinergic, and serotoninergic nerves were studied in the myenteric plexus of ileum and colon from streptozotocin-treated rats, an animal model of juvenile-onset diabetes. In view of clinical reports implicating diabetic autonomic neuropathy as the cause of gastrointestinal dysfunction in diabetes mellitus, neurochemical and histochemical techniques were used to study changes in the innervation of the gut. In the myenteric plexus of the ileum from diabetic animals, adrenergic nerves displayed signs of degeneration and the brightness of fluorescence in serotoninlike immunoreactive nerves was lower. Cholinergic nerves, however, did not display any signs of reduction in the ileum, and both choline acetyltransferase and acetylcholinesterase activities per centimeter were increased. In contrast, in the proximal colon 8 wk after induction of diabetes, neurochemical assays revealed significant increases in noradrenaline and serotonin levels as well as choline acetyltransferase activity, although no obvious changes in the pattern of innervation could be detected histochemically. The results indicate that changes do occur in the innervation of the gut of the streptozotocin-diabetic model shortly after the induction of diabetes, although they differ significantly in the ileum and colon; these may be of relevance to the types of gastrointestinal dysfunction displayed in human diabetes.
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PMID:Myenteric plexus in streptozotocin-treated rats. Neurochemical and histochemical evidence for diabetic neuropathy in the gut. 669 66

Autonomic neuropathy is a common complication of diabetes mellitus, and both morphological and physiological data suggest that salivary gland function in diabetic rats is affected by neuropathies involving sympathetic and parasympathetic nerves. Therefore, glandular levels of the adrenergic neurotransmitter, norepinephrine (NE) and two cholinergic enzymes, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), were investigated in 6-month streptozotocin-diabetic rats. Significant, but variable, increases in total parotid NE (ng/gland) were observed in diabetic rats, whereas total submandibular NE was lower in diabetic animals than in controls. However, on a ng/mg tissue basis, NE levels in both the parotid gland, and less dramatically, in the submandibular gland were increased. Somewhat different results were observed for AChE and ChAT. AChE was marginally greater in the parotid glands of diabetic rats, whereas AChE and ChAT levels were significantly lower in diabetic than control submandibular glands. Expressed as enzymatic activity per mg tissue, submandibular gland ChAT, but not AChE, was increased. Short-term (3-day) insulin treatment of diabetic animals had no significant effects on total NE, AChE or ChAT in the parotid gland, but led to a further reduction in submandibular ChAT. With regard to function, changes in AChE appeared to be correlated with previously reported morphological assessments of parotid gland innervation in diabetic animals. Thus, the decreased response of the parotid gland in diabetic rats to parasympathetic stimulation may be related in part to the increase in AChE.
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PMID:The effects of streptozotocin-induced diabetes on norepinephrine and cholinergic enzyme activities in rat parotid and submandibular glands. 818 4

The distribution of adrenergic, cholinergic and amino acid neurotransmitters and/or their enzymes were examined in both the normal and diabetic pancreatic tissues in rat using immunohistochemistry to determine whether changes in the pattern of distribution of nerves containing these neurotransmitters will occur as a result of diabetes mellitus. In addition to this, the effect of noradrenaline (NA), adrenaline (ADR), acetylcholine (ACh) and gamma-amino butyric acid (GABA) on glucagon secretion from the isolated normal and diabetic pancreatic tissues was also investigated. Pancreatic fragments from the tail end of normal and diabetic rats were removed and incubated with different concentrations (10(-8)-10(-4) M) of these neurotransmitters. Glucagon secretion into the supernatant was later determined by radioimmunoassay. NA at 10(-6) M evoked a three-fold increase in glucagon secretion from normal pancreatic tissue fragments. In diabetic pancreatic tissue, NA at 10(-6) M was able to increase glucagon secretion 1.5 times the value obtained from diabetic basal. ADR (10(-8) M) increased glucagon secretion slightly but not significantly in normal pancreatic tissue. ADR inhibited glucagon secretion from diabetic pancreas at all concentrations. ACh (10(-8) M) induced a five-fold increase in glucagon secretion from normal pancreatic tissue. In a similar way, ACh evoked a two-fold increase in glucagon secretion from diabetic pancreas at 10(-4) M. In normal pancreatic tissue, GABA produced a slight but not significant increase in glucagon secretion at 10(-4) M. In contrast to this it inhibited glucagon secretion from diabetic pancreatic tissue fragments at all concentrations. In summary, tyrosine hydroxylase- and choline acetyltransferase-positive nerves are equally well distributed in both normal and diabetic rat pancreas. There was an increase in the number of glucagon positive cells and a decrease in the number of GABA-positive cells in diabetic pancreas. NA and ACh have a potent stimulatory effect on glucagon secretion from normal pancreatic tissue fragments, whereas ADR and GABA produced a small but not significant increase in glucagon secretion from normal pancreas. NA and GABA stimulated glucagon secretion from diabetic pancreas. In contrast, ADR and ACh inhibited glucagon secretion from diabetic pancreas. Neurotransmitters vary in their ability to provoke glucagon secretion from either normal or diabetic pancreas.
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PMID:Distribution of neurotransmitters and their effects on glucagon secretion from the in vitro normal and diabetic pancreatic tissues. 1103 98

Neurotrophic factors (NFs) are promising agents for the treatment of peripheral neuropathies such as diabetic neuropathy. However, the value of treatment with recombinant NF is limited by the short half-lives of these molecules, which reduces efficiency, and by their potential toxicity. We explored the use of intramuscular injection of a recombinant adenovirus encoding NT-3 (AdNT-3) to deliver sustained low doses of NT-3. We assessed its effect in two rat models: streptozotocin (STZ)-induced diabetes, a model of early diabetic neuropathy characterized by demyelination, and acrylamide experimental neuropathy, a model of diffuse axonal neuropathy which, like late-onset human diabetic neuropathy, results in a diffuse sensorimotor neuropathy with dysautonomy. Treatment of STZ-diabetic rats with AdNT-3 partially prevented the slowing of motor and sensory nerve conduction velocities (p < 0.01 and p < 0.0001, respectively). Treatment with AdNT-3 of acrylamide-intoxicated rats prevented the slowing of motor and nerve conduction velocities (p < 0.001 and p < 0.0001, respectively) and the decrease in amplitude of compound muscle potentials (p < 0.0001), an index of denervation. Acrylamide-intoxicated rats treated with NT-3 had higher than control levels of muscle choline acetyltransferase activity (p < 0.05), suggesting greater muscle innervation. In addition, treatment of acrylamide-intoxicated rats with AdNT-3 significantly improved behavioral test results. Treatment with AdNT-3 was well tolerated with minimal muscle inflammation and no detectable general side effects. Therefore, our results suggest that NT-3 delivery by adenovirus-based gene therapy is a promising strategy for the prevention of both early diabetic neuropathy and axonal neuropathies, especially late axonal diabetic neuropathy.
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PMID:Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies. 1177 7

Significant progress in the field of VaD resulted from publication of the NINIDS-AIREN Diagnostic Criteria for VaD (G.C. Roman, T.K. Tatemichi, T. Erkinjuntti, et al., Vascular dementia (VaD): diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43 (1993) 250-260). Epidemiological studies confirmed the importance of VaD as the second most common cause of dementia in the elderly, representing 15-20% of all cases of dementia. In Europe and North America, Alzheimer's disease (AD) predominates over VaD in a 2:1 ratio; in contrast, in Japan and China VaD accounts for almost 50% of all dementias. Case-control studies have identified risk factors for VaD including ageing, hypertension, diabetes mellitus, hyperlipidemia, recurrent stroke, cardiac disease, smoking, sleep apnea, and more recently, hyperhomocysteinemia, among others. Hypertension treatment may prevent VaD and AD. This finding has enormous importance from the Public Health viewpoint to decrease the future number of patients with dementia in the elderly. Along with advances in the field of VaD came a number of controversies and damaging misconceptions and myths. Myth no. 1--Vascular dementia is a non-entity: The false idea that VaD does not exist is particularly destructive because it creates the perspective that VaD is unworthy of study or research. A condition that either does not exist or represents only a minute proportion of all cases of dementia in the elderly, lacks public health relevance and becomes a low priority for research by funding agencies and industry. In fact, vascular brain lesions are the commonest and most important component of dementia in the elderly. Myth no. 2--Vascular dementia is so difficult to diagnose that only experts can recognize and identify it accurately: VaD does exist and the diagnosis of post-stroke VaD, in particular is straightforward. Most cases fulfill NINDS-AIREN criteria for probable VaD; i.e., (1) there is acute onset of dementia demonstrated by impairment of memory and two other cognitive domains, such as orientation, praxis or executive dysfunction; (2) relevant cerebrovascular lesions are demonstrated by neuroimaging; and (3) a temporal relation between stroke and cognitive loss is evident. In the donepezil trials on VaD, post-stroke dementia represented about 75% of the >1,200 patients enrolled. Myth no. 3--Improvement in clinical trials of cholinergics in VaD is due to underlying AD, not to the vascular lesions. Experimental, clinical and pathological evidence has demonstrated cholinesterase deficits in VaD (independently of any concomitant AD pathology), including low acetylcholine in cerebrospinal fluid, and reduced choline acetyltransferase (ChAT) in the brain.
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PMID:Facts, myths, and controversies in vascular dementia. 1553 19


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