Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine whether deficient substance P in the sciatic nerve of diabetic rats was associated with a similar reduction in calcitonin gene-related peptide and whether the depletion of either or both peptides could be affected by insulin treatment or by aldose reductase inhibition. Substance P and calcitonin gene-related peptide were measured as immunoreactivities in the same nerve extracts. The sciatic nerve content of substance P was significantly reduced in diabetic rats (0.063 +/- 0.011; all data are mean +/- 1 standard deviation in ng peptide/mg nerve protein; n = 9 for all groups) compared to controls (0.093 +/- 0.026). The calcitonin gene related peptide content was similarly reduced (2.14 +/- 0.49) compared to controls (3.78 +/- 1.21). Tight glycaemic control with insulin prevented completely the deficit in both peptides (substance P = 0.096 +/- 0.021, calcitonin gene-related peptide = 4.66 +/- 0.92). Treatment with the aldose reductase inhibitor, imirestat, corrected the substance P deficit (0.08 +/- 0.018) and attenuated the calcitonin gene-related peptide (3.55 +/- 1.03) depletion seen in the untreated diabetic animals. This indicates that the polyol pathway may play a role in the peptide status of the sciatic nerve. Regression analysis of all data gave r2 = 0.53, indicating a comparable effect of diabetes and the treatments on both peptides.
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PMID:Depletion of substance P and calcitonin gene-related peptide in sciatic nerve of rats with experimental diabetes; effects of insulin and aldose reductase inhibition. 137 69

This study examined the axonal transport of substance P-like immunoreactivity (SPLI) and its content in dorsal root ganglion, trigeminal ganglion, stomach and ileum of non-diabetic rats and two groups of rats with streptozotocin-induced diabetes of 9 months duration. One diabetic group received the aldose reductase inhibitor 'Statil' throughout the period of study. To reduce morbidity all diabetic animals were given twice-weekly injections of a long-acting insulin which restricted weight loss but did not prevent regular and severe hyperglycaemia. Axonal transport of SPLI was studied by measurement of accumulation at 12 h ligatures on the left sciatic nerve. There were no differences between the 3 groups either in the calculated anterograde and retrograde mean rates of accumulation (ranges 6.0 to 7.6 and 0.38 to 0.72 mm/h respectively) or mobile fractions of SPLI (means from 0.54 to 0.58). There were, however, marked reductions in anterograde and retrograde accumulations of SPLI in the constricted nerves of the 'untreated' diabetics (respectively 57 and 33% of controls; P less than 0.01 for both). In the 'Statil'-treated rats these deficits were attenuated (80 and 75% of controls). Diabetes also reduced the SPLI content of unligated sciatic nerve and trigeminal ganglion (65 and 75% of controls). 'Statil' prevented the deficit in the ganglion, but not in the nerve. 'Statil' treatment prevented the myo-inositol depletion and attenuated the sorbitol and fructose accumulation seen in the sciatic nerves of the untreated diabetic animals suggesting effective inhibition of aldose reductase in this tissue. The total SPLI content of the stomach and 1-cm segments of ileum were unaltered in the diabetic animals but due to the increased weights of these tissues the SPLI content per unit weight was reduced. These changes were unaffected by 'Statil'.
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PMID:Axonal transport and tissue contents of substance P in rats with long-term streptozotocin-diabetes. Effects of the aldose reductase inhibitor 'statil'. 244 12

This study measured the accumulation of substance P-like immunoreactivity (SPLI) proximal and distal to 12-h constricting ligatures applied to rat sciatic nerves. There were three separate experiments, and the baseline for each consisted of control and age-matched rats with 3 wk of untreated streptozocin-induced diabetes. We compared the effects of twice-daily insulin treatment, daily sorbinil (25 mg.kg-1.day-1 p.o.), and a combination of both treatments. In untreated diabetic rats the anterograde accumulation of SPLI was reduced by 30-40%. This deficit was unaffected by sorbinil alone but was attenuated by insulin and prevented completely by insulin and sorbinil combined. There were also indications that diabetes caused reductions in retrograde accumulation of SPLI and its content in unconstricted nerve and the L4 dorsal root ganglion. The fraction of SPLI undergoing net anterograde or retrograde movement and the velocities of accumulation were unaffected by diabetes or the treatment regimens. These findings indicate a reduction in the amount of substance P moved by axonal transport in diabetic rats that is related partly to aldose reductase activity and partly to some other insulin-correctable consequence of experimental diabetes.
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PMID:Deficient axonal transport of substance P in streptozocin-induced diabetic rats. Effects of sorbinil and insulin. 245 10

This study was performed on male Wistar rats with streptozotocin-induced diabetes mellitus of 11 months duration. There were two diabetic groups; both were given a long-acting insulin twice weekly to reduce morbidity. One group received no additional treatment whilst the other was given the aldose reductase inhibitor, sorbinil, by dietary admixture (approximate dose was 30 mg/day/kg body weight). At the end of the protocol the lenses of the diabetic rats given insulin alone showed markedly reduced dry weight (70% of controls; p less than 0.01) with increased water content (152% of controls; p less than 0.01). Both of these changes were absent from the lenses of the sorbinil-treated diabetic rats. Lenses from both groups of diabetic rats had elevated glucose contents, with greater levels in the group which received insulin alone. Polyol pathway metabolites were also raised in the diabetic lenses, though sorbinil treatment had markedly attenuated sorbitol accumulation without affecting fructose levels. Lens myo-inositol was almost absent from the diabetic rats which received only insulin (6% of control levels relative to lens dry weight; p less than 0.01). This depletion was substantially attenuated, but not prevented in the sorbinil-treated group (58% of control levels). In the iris the noradrenaline and adrenaline contents were unaltered in either diabetic group. In startling contrast, the iris content of substance P-like immunoreactivity was almost trebled in the insulin alone-treated diabetic rats (282% of controls; p less than 0.01), an effect which was prevented completely by sorbinil (127% of controls; not significantly different).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of sorbinil treatment in rats with chronic streptozotocin-diabetes; changes in lens and in substance P and catecholamines in the iris. 247 May 51

This study measured the content of substance P-like immunoreactivity (SPLI) in peripheral nervous tissue (lumbar dorsal root ganglia, sciatic nerve), skin (snout, foot), gastrointestinal tract (stomach, terminal ileum) and in the atria of the heart. Animals studied were long-term (11 months) streptozotocin-diabetic rats compared with age-matched control rats. All diabetic rats were given a very long acting insulin preparation twice weekly to reduce morbidity. Half of the diabetic rats were given the aldose reductase inhibitor, sorbinil (mean dose 30 mg/kg/day body weight by dietary admixture) over the entire protocol. Diabetic rats (given insulin only) showed marked accumulation of sorbitol and fructose together with myo-inositol depletion in their sciatic nerves. The sciatic nerves of the sorbinil-treated diabetic rats contained amounts of sorbitol, fructose and myo-inositol which were similar to those of non-diabetic rats, in spite of large amounts of nerve glucose in the sorbinil-treated animals. Thus, the inhibition of aldose reductase was successful. The L4 and L5 dorsal root ganglia of the diabetic rats showed reduced SPLI (63% and 72% respectively of control ganglia; P less than 0.05). There was also numerical reduction in sciatic nerve SPLI (84% of control nerve). There were no effects of sorbinil treatment on the reduced SPLI levels in ganglia or sciatic nerve. In the gastrointestinal tract the levels of SPLI were reduced in diabetic rats even when data were adjusted to take account of tissue hypertrophy (diabetic SPLI/whole stomach was 60% controls, P less than 0.01 and SPLI/cm ileum was 78%, though the latter did not attain statistical significance). In skin SPLI/unit area was raised in the diabetic rats to 145% of controls for foot skin and 151% for snout skin. Changes in SPLI content of gastrointestinal tract were unaffected by sorbinil treatment; in the skin the elevations were enhanced to 188% and 270% of respective control values for foot and snout skin. The SPLI content of the atria was unaffected by diabetes or sorbinil. These data are not consistent with a generalised impairment of delivery of substance P by axonal transport in experimental diabetes; special factors appear to influence the levels in neurones innervating different tissues. Exaggerated flux through the polyol pathway appears to be uninvolved.
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PMID:Substance P levels in peripheral nerve, skin, atrial myocardium and gastrointestinal tract of rats with long-term diabetes mellitus. Effects of aldose reductase inhibition. 247 71

The aim of the present study was to determine whether diabetes-induced changes in the distribution of enteric neuropeptides, could be prevented in 12-week streptozotocin-diabetic rats, by rigorous control of glycaemia, using daily adminstration of insulin, or an aldose reductase inhibitor (ponalrestat). The pattern of distribution of nerve fibres and cell bodies, containing immunoreactive vasoactive intestinal polypeptide (VIP), galanin (GAL), calcitonin gene-related peptide (CGRP) and substance P was examined in the myenteric plexus of ileum from control, untreated diabetic, insulin-treated diabetic and aldose reductase inhibitor-treated diabetic rats. The increase in VIP- and GAL-like immunoreactivity, seen in the myenteric plexus of untreated diabetic rat ileum, was not present in the myenteric plexus of ileum from insulin- and aldose reductase inhibitor-treated diabetic rats. With CGRP-like immunoreactive fibres, there was a clear decrease in the ileum of untreated diabetic rats. This was prevented by insulin treatment, but aldose reductase inhibitor treatment had no effect. No alterations in substance P-like immunoreactivity were seen in the myenteric plexus of ileum from any of the groups investigated. Generally, the similarity of effect of ponalrestat and insulin on VIP and galanin expression in this study supports a primary effect of insulin via glycaemic control. The dissimilarity of the effect of the two treatments on CGRP expression may imply a neurotrophic effect of insulin, although there are certainly consequences of hyperglycaemia other than exaggerated flux through the polyol pathway.
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PMID:Enteric neuropeptides in streptozotocin-diabetic rats; effects of insulin and aldose reductase inhibition. 873 9

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P < 0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P < 0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NFG, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes--a mechanism that might participate in iritis.
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PMID:Stimulation of nerve growth-factor and substance P expression in the iris-trigeminal axis of diabetic rats--involvement of oxidative stress and effects of aldose reductase inhibition. 974 8

We explored the specific impact of polyol pathway hyperactivity on dorsal root ganglia (DRG) using transgenic mice that overexpress human aldose reductase because DRG changes are crucial for the development of diabetic sensory neuropathy. Littermate mice served as controls. Half of the animals were made diabetic by streptozotocin injection and followed for 12 weeks. After diabetes onset, diabetic transgenic mice showed a significant elevation of pain sensation threshold after transient decrease and marked slowing of motor and sensory nerve conduction at the end of the study, while these changes were modest in diabetic littermate mice. Protein kinase C (PKC) activities were markedly reduced in diabetic transgenic mice, and the changes were associated with reduced expression of membrane PKC-alpha isoform that was translocated to cytosol. Membrane PKC-betaII isoform expression was contrariwise increased. Calcitonin gene-related peptide-and substance P-positive neurons were reduced in diabetic transgenic mice and less severely so in diabetic littermate mice. Morphometric analysis disclosed neuronal atrophy only in diabetic transgenic mice. Treatment with an aldose reductase inhibitor (fidarestat 4 mg x kg(-1) x day(-1), orally) corrected all of the changes detected in diabetic transgenic mice. These findings underscore the pathogenic role of aldose reductase in diabetic sensory neuropathy through the altered cellular signaling and peptide expressions in DRG neurons.
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PMID:Effects of polyol pathway hyperactivity on protein kinase C activity, nociceptive peptide expression, and neuronal structure in dorsal root ganglia in diabetic mice. 1556 56