Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45-65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF-transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time.
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PMID:Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation. 185 52

Sympathetic and neural-crest derived sensory neurons consisting of unmyelinated and small myelinated fibers are known to be affected at an early stage in diabetes mellitus (DM). Since these peripheral neurons need nerve growth factor (NGF) for their development and maintenance of function in adulthood, changes in endogenous NGF levels could be of relevance for the pathogenesis of diabetic neuropathy (DNP). Using an improved two-site enzyme immunoassay for NGF, we have investigated whether endogenous NGF levels are altered in Sprague-Dawley rats with DM induced by a single injection of streptozotocin (STZ). STZ-treated rats are known to develop in many respects equivalents to neuropathic complications observed in human DM. We found in some sympathetically innervated target organs decreased NGF contents by maximally 56%: transiently in the iris 2 weeks and in the ventricle 12-24 weeks after DM induction and permanently in the submandibular gland already 3 days after DM induction. Several weeks after onset of DM, NGF content was increased by maximally 145-300% in most peripheral targets investigated, such as in iris, cardiac atrium and ventricle, spleen, prostate gland, and vas deferens. This is suggestive for an impaired NGF removal by NGF-sensitive neurons in diabetic rats. Moreover, NGF levels were decreased to minimally 42.6 +/- 4% of control in the NGF-transporting sciatic nerve. NGF levels began to decrease not before 3 weeks after DM induction and remained decreased with 54.0 +/- 5% of control even after 6 months duration of DM. About the same time (i.e., 2 weeks after induction of DM) NGF levels began to decrease in the superior cervical ganglion (where the sympathetic perikarya are located) to minimally 53.2 +/- 4% of control 12 weeks after DM induction. No altered NGF levels were observed during a 3-month duration of DM in the terminal ileum and sensory trigeminal ganglion. Since NGF exerts its neurotrophic action in the perikarya after its retrograde transport from the NGF-producing periphery, our results are consistent with the hypothesis that an alteration in NGF levels may play a role in the pathogenesis of DNP as far as sympathetic neurons are concerned. Thus, our results suggest that DM influences the production and/or transport of endogenous NGF and consequently, that a deprivation of this neurotrophic factor may account for some of the functional deficits known to occur in DNP, such as impaired catecholaminergic transmitter synthesis. This hypothesis possibly opens the way for new concepts in the therapy of DNP.
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PMID:Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy. 214 24

Several structural and functional similarities between nerve growth factor and insulin have been described. Diabetes mellitus, a disease with absolute or relative deficiency of insulin is frequently associated with peripheral neuropathy whose physiopathological mechanisms are obscure. In this study, we measured serum levels of NGF in 18 patients with diabetic neuropathy and 9 healthy controls; patients with diabetic neuropathy had lower levels of NGF than controls (p less than 0.01). When patients were separated in two groups according to degree of impairment of motor nerve conduction velocity, those with more than 10% of impairment, had lower levels of NGF than those with less than 10% of impairment, or controls. It was found a correlation between NGF levels and decrease of motor nerve conduction velocity; then, diabetic neuropathy seems to be associated to low serum levels of NGF, pointing out a possible role of NGF in the pathology of diabetic neuropathy.
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PMID:Low serum levels of nerve growth factor in diabetic neuropathy. 237 41

We have previously demonstrated the reproducible occurrence of dystrophic axonopathy and a defect in the retrograde axonal transport of 125I-nerve growth factor (125I-NGF) involving postganglionic sympathetic axons in the alimentary tract of rats with chronic streptozocin (STZ)-induced diabetes. To avoid complexities inherent in monitoring the accumulation of 125I-NGF in the superior mesenteric ganglion as a measure of retrograde transport in the peripheral axons of the extensive alimentary territory, we have examined retrograde axonal transport of 125I-NGF directly in ileal mesenteric nerves. 125I-NGF was injected systemically, and 2-2.5 h later ileal mesenteric nerve pedicles were ligated in vivo for various intervals. Retrogradely transported 125I-NGF in rat mesenteric nerves was measured distal to a ligature placed on the ileal mesenteric pedicle. Transport-unrelated processes, such as mechanical compression or bleeding at the site of ligation, did not contribute significantly to accumulation measured in this fashion. Accumulation of retrogradely transported 125I-NGF at the ligature began 4 h after ligation and remained linear for approximately 12 h. The amount of retrogradely transported 125I-NGF accumulating distal to the ligature reflected the length of the ileal segment served by the pedicle, which allowed the standardization of accumulation based on length of ileum innervated. The results of several experiments showed that 125I-NGF transport originated largely from nerve terminals within the ileal wall with a smaller component from extramural sites, probably terminals within the walls of blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Dec
PMID:Retrograde axonal transport in rat ileal mesenteric nerves. Characterization using intravenously administered 125I-nerve growth factor and effect of chemical sympathectomy. 241 13

The retrograde axonal transport of intravenously (i.v.) administered 125I-nerve growth factor (125I-NGF) was examined in mesenteric nerves innervating the small bowel of rats with streptozocin (STZ) diabetes using methods described in detail in the companion article. The accumulation of 125I-NGF distal to a ligature on the ileal mesenteric nerves of diabetic animals was 30-40% less than in control animals. The inhibition of accumulation of 125I-NGF in diabetic animals was greater at a ligature tied 2 h after i.v. administration than at a ligature tied after 14 h, which suggests that the diabetic animals may have a lag in initiation of NGF transport in the terminal axon or retardation of transport at some site along the axon. The 125I-NGF transport defect was observed as early as 3 days after the induction of diabetes, a time before the development of structural axonal lesions, and did not worsen at later times when dystrophic axonopathy is present. Both the ileal mesenteric nerves, which eventually develop dystrophic axonopathy in experimental diabetes, and the jejunal mesenteric nerves, which never develop comparable structural alterations, showed similar 125I-NGF transport deficits, suggesting that the existence of the transport abnormality does not predict the eventual development of dystrophic axonal lesions. Autoradiographic localization of 125I-NGF in the ileal mesenteric nerves of animals that had been diabetic for 11-13 mo demonstrated decreased amounts of 125I-NGF in transit in unligated paravascular nerve fascicles. There was, however, no evidence for focal retardation of transported 125I-NGF at the sites of dystrophic axonal lesions.
Diabetes 1985 Dec
PMID:Retrograde axonal transport of 125I-nerve growth factor in rat ileal mesenteric nerves. Effect of streptozocin diabetes. 241 14

The retrograde axonal transport of intravenously administered [125I]nerve growth factor ([125I]NGF) was examined in ileal mesenteric nerves maintained for short periods in vitro. [125I]NGF was injected systemically, and at various times thereafter mesenteric pedicles were ligated and incubated in vitro in Krebs-Henseleit medium under a number of different conditions. Retrogradely transported [125I]NGF began to accumulate distal to the ligature after an initial lag period and increased in a linear fashion for 3-4 h. The amount of retrogradely transported [125I]NGF was proportional to the length of the ileum innervated by each pedicle, which allowed for comparison of ileal segments of different lengths. Retrograde axonal transport of [125I]NGF was inhibited by vinblastine, colchicine and incubation in the cold, and was decreased by agents that interfere with oxidative or glycolytic metabolism. The accumulation of retrogradely transported [125I]NGF in ileal mesenteric nerves of 1-9 day streptozotocin diabetic animals placed in an in vitro bath containing normal (5.5 mM) glucose was decreased 40% compared to control animals. The induction of diabetes in vivo resulted in a greater decrease in the early phases of [125I]NGF export from ileal mesenteric nerve terminals compared to later phases. Ileal mesenteric nerve segments derived from untreated controls were incubated in vitro in media containing increased concentrations of glucose (27.5 and 50 mM) without reproducing the NGF transport defect found in diabetic animals.
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PMID:Retrograde axonal transport of [125I]nerve growth factor in ileal mesenteric nerves in vitro: effect of streptozotocin diabetes. 242 4

We have previously demonstrated a reproducible axonopathy, involving but not confined to sympathetic neurons, which involves selectively the mesenteric nerves of chronically diabetic rats. We describe a series of experiments aimed at correlating changes in the retrograde transport of 125I-nerve growth factor (125I-NGF) with development of the lesions. 125I-NGF was injected systemically and the time course of accumulation compared in superior cervical ganglion (SCG) and superior mesenteric ganglion (SMG). 125I-NGF accumulated in the SCG with a sharp peak at 12 h, whereas in the SMG, accumulation reached a plateau, remaining at relatively constant amounts for 8 h before decreasing. There was a marked decrease in the accumulation of 125I-NGF (averaging 44% in 11 separate experiments) in the SMG at early times (approximately 12 h). These decreases were seen in animals diabetic for times ranging from 2 days to 10 mo. In contrast, no consistent decrease was observed in the SCG. The time course of 125I-NGF accumulation was unaltered in the SCG of diabetic rats but was clearly retarded in the SMG of diabetic animals. Morphometric examination of the SMG of diabetic animals and controls showed little or no atrophy or neuron loss due to diabetes. We conclude that decreases in the retrograde transport of NGF occur selectively in those ganglia (SMG) serving the alimentary tract in which mesenteric nerves develop distal axonopathy, but not in ganglia whose nerves do not ultimately develop such lesions (SCG). The decreases in retrograde transport precede the development of morphologic lesions in this system. These results are consistent with the suggestion that impairment of axonal transport may play a role in the development of axonopathy.
Diabetes 1983 Jul
PMID:Retrograde axonal transport of intravenously administered 125I-nerve growth factor in rats with streptozotocin-induced diabetes. 634 45

Rats with streptozotocin-induced diabetes of 4 to 6 weeks duration showed a depletion of both substance P (P < 0.01) and calcitonin gene-related peptide (P < 0.01) in the sciatic nerve. Since expression of both peptides is sensitive to nerve growth factor (NGF) in vitro we examined the effect of treatment of diabetic rats with NGF, which significantly increased the levels of both peptides in treated diabetic animals (P < 0.01 for both). Treatment of non-diabetic rats with a similar NGF regime raised the mean peptide levels to a value similar to that seen in treated diabetic rats but the change was not statistically significant. In vehicle-treated diabetic rats the depletions of sciatic nerve neuropeptides were accompanied by a significant (P < 0.05) reduction in the level of CGRP mRNA in the 4th and 5th lumbar dorsal root ganglia, this was accompanied by an analogous reduction in the mRNA for gamma-preprotachykinin A (gamma-PPT), which did not attain statistical significance. Treatment of diabetic rats with NGF also prevented the deficits in the levels of CGRP and gamma-PPT mRNA in the lumbar dorsal root ganglia (P < 0.05). Treatment of other diabetic rats with the related neurotrophin, brain-derived neurotrophic factor (BDNF), had no effect on the levels of substance P and calcitonin gene-related peptide in the sciatic nerve.
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PMID:Expression of neuropeptides in experimental diabetes; effects of treatment with nerve growth factor or brain-derived neurotrophic factor. 751 41

Dorsal root ganglion neurons from streptozotocin (STZ)-induced diabetic, genetic diabetic and normal mice were cultured in serum-containing media with or without nerve growth factor (NGF). The immunocytochemical analysis carried out after 1 week in culture revealed that the ratios of neurons immunoreactive to calcitonin gene-related peptide (CGRP) in NGF-free medium in the STZ-diabetic mice (average 23.2%) were significantly lower than those in the normal mice (45.1%). The ratios of neurons immunoreactive to CGRP and substance P (SP) in the NGF-free medium were also lower in the genetic diabetic mice (23.6% and 21.8%) than those in the normal ones (40.7% and 34.2%). However, treatment with NGF restored these reduced immunoreactivities in the diabetic groups in a dose-dependent manner. These results show that NGF can be effective for the diabetes-induced depletion of CGRP and SP in sensory neurons, and suggest its possible role in the prevention and improvement of diabetic sensory neuropathy.
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PMID:Nerve growth factor (NGF) restores depletions of calcitonin gene-related peptide and substance P in sensory neurons from diabetic mice in vitro. 753 Jul 67

This study was designed to explore effects of experimental diabetes mellitus on expression of substance P in the trigeminal ganglion and of nerve growth factor (NGF) in the iris. Rats with streptozotocin-diabetes showed an increase in NGF mRNA in the iris (P < 0.01) which was corrected by insulin treatment. There was also an increase in the levels of mRNA for the substance P precursor, preprotachykinin (PPT), in the trigeminal ganglion of these animals, despite there being no change in GAP-43 mRNA. Since expression of both of these peptides is sensitive to NGF in vitro, we examined the effect of treatment of diabetic rats with NGF at three different doses (0.2, 0.5 and 1.0 mg/kg body weight). There was a dose-dependent increase in both gamma-PPT and GAP-43 mRNA in the trigeminal ganglia of NGF-treated diabetic rats. The findings indicate that increased NGF may be responsible for raised substance P levels in the iris.
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PMID:Changes in nerve growth factor and preprotachykinin messenger RNA levels in the iris and trigeminal ganglion in diabetic rats; effects of treatment with insulin or nerve growth factor. 776 88


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