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

Sensory deficits induced by diabetes commonly affect small unmyelinated peptidergic and nonpeptidergic sensory neurons. The peptidergic population responds to nerve growth factor (NGF), while the nonpeptidergic DRG neurons postnatally switch their dependency from NGF to glial cell line-derived neurotrophic factor (GDNF). Recent studies have demonstrated that deficient NGF support of peptidergic nociceptors is involved in problems with small-fiber diabetic neuropathy. To determine if nonpeptidergic GDNF-responsive neurons are similarly affected by hyperglycemia, diabetes was induced in mice using streptozotocin (STZ). Four weeks following diabetes induction, staining of axon terminals of nonpeptidergic unmyelinated neurons labeled with the isolectin IB4 or enzyme activity for thiamine monophosphatase (TMP) was reduced in lamina IIi of the lumbar dorsal horn, particularly in the medial region which receives distal sciatic afferents. In contrast, NGF-responsive CGRP-immunoreactive (ir) axons showed no or only a slight decrease in spinal terminations. Insulin treatment in diabetic mice failed to improve deficits in IB4/TMP central afferents. To test whether GDNF or NGF could restore spinal deficits in nonpeptidergic afferents, STZ-treated mice were treated intrathecally for 2 weeks with NGF or GDNF. NGF administration enhanced CGRP-ir staining but failed to improve IB4/TMP projections. GDNF treatment had no effect on CGRP-ir projections but restored TMP labeling in lamina IIi. Our results demonstrate that nonpeptidergic unmyelinated sensory neurons are vulnerable to diabetes and that GDNF administration can selectively reverse deficits caused by diabetes in the IB4/TMP subpopulation.
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PMID:GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice. 1116 5

As HIV and AIDS patients live longer, more neurologic disorders are being reported that require prompt identification and treatment. Neuropathies can be caused by nutritional deficiencies, antiretroviral or chemotherapy drugs, certain toxins such as alcohol, and coexistance of other illnesses such as diabetes. Each of the following neuropathies is discussed: distal painful neuropathy, Guillain-Barre Syndrome, mononeuropathy, cytomegalovirus-related neuropathy, and diabetes. Treatment options are also examined, including practical measures, and results from clinical studies evaluating the efficacy of amitriptyline, mexiletine, acupuncture, and nerve growth factor for neuropathic pain.
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PMID:Peripheral neuropathy. 1136 22

Abnormal availability of neurotrophins, such as nerve growth factor (NGF), has been implicated in diabetic somatosensory polyneuropathy. However, the involvement of neurotrophins in diabetic neuropathy of autonomic nerves, particularly the vagus nerve which plays a critical role in visceral afferent and in autonomic motor functions, is unknown. To assess the effects of hyperglycemia on the neurotrophin content and transport in this system, cervical vagus nerves of streptozotocin (STZ)-induced diabetic rats were studied at 8, 16, and 24 weeks after the induction of diabetes. Elevations in vagus nerve hexose (glucose and fructose) and polyol levels (sorbitol), and their normalization with insulin treatment, verified that the STZ treatment resulted in hyperglycemia-induced metabolic abnormalities in the nerve. Neurotrophin (NGF and neurotrophin-3; NT-3) content and axonal transport were assessed in the cervical vagus nerves from nondiabetic control rats, STZ-induced diabetic rats, and diabetic rats treated with insulin. The NGF, but not the NT-3, content of intact vagus nerves from diabetic rats was increased at 8 and 16 weeks (but not at 24 weeks). Using a double-ligation model to assess the transport of endogenous neurotrophins, the retrograde transport of both NGF and NT-3 was found to be significantly reduced in the cervical vagus nerve at later stages of diabetes (16 and 24 weeks). Anterograde transport of NGF or NT-3 was not apparent in the vagus nerve of diabetic or control rats. These data suggest that an increase in vagus nerve NGF is an early, but transient, response to the diabetic hyperglycemia and that a subsequent reduction in neuronal access to NGF and NT-3 secondary to decreased retrograde axonal transport may play a role in diabetes-induced damage to the vagus nerve.
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PMID:Streptozotocin-induced diabetes causes metabolic changes and alterations in neurotrophin content and retrograde transport in the cervical vagus nerve. 1142 92

It has been suggested that insulin has an effect on nerve regeneration similar to that of nerve growth factor (NGF). Therefore, we aimed to evaluate the effectiveness of local insulin injection on median nerve in patients with non-insulin-dependent diabetes (NIDDM) mellitus who have mild-to-moderate carpal tunnel syndrome (TS). We carried out a prospective, randomized, double-blind, placebo-controlled study in these patients. At the baseline, 20 mg methylprednisolone was injected directly into the carpal tunnel in all patients [n=43 (62 hands)]. A week after prednisolone, the placebo or NPH insulin (12 U) was injected into the carpal tunnel weekly for 7 weeks. The patients were followed up for 23 weeks. A significant improvement in mean median nerve motor distal latency (MNMDL), median nerve sensory velocity (MNSV), and global symptom score (GSS) occurred in both groups (with the exception of mean MNMDL in the placebo group). A more significant improvement in the mean MNMDL, MNSV, and GSS was observed in the insulin group when compared with the placebo group. This study suggests that local insulin treatment may be of great potential benefit in the improvement of nerve functions in NIDDM patients with mild-to-moderate CTS who opt for conservative treatment.
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PMID:Local insulin injection improves median nerve regeneration in NIDDM patients with carpal tunnel syndrome. 1142 29

We analyzed the effect of a brief exposure to nerve growth factor (NGF) on insulin secretion and macroscopic barium currents of single adult rat pancreatic beta-cells. After a 1-h exposure to NGF (50 ng/ml), single beta-cells show a 2.5-fold increase in the insulin secretion index in 5.6 mmol/l glucose and a nearly twofold increase in 15.6 mmol/l glucose compared with control cells. We have recently demonstrated that pancreatic beta-cells synthesize and secrete NGF. We analyzed the effect of endogenous NGF on insulin secretion by incubating islet cells in the presence of an anti-NGF monoclonal antibody for 1 h in different glucose concentrations. Although the basal insulin secretion index (5.6 mmol/l glucose) is not affected, glucose-stimulated insulin secretion (15.6 mmol/l glucose) is decreased by 41% in the presence of the antibody. This effect is mediated by the activation of the NGF receptor TrkA because the specific inhibitor of Trk phosphorylation K252a also blocks NGF-induced increase in insulin secretion, both in the presence and absence of exogenous NGF. Using the whole-cell variation of the patch-clamp technique, we found that cells exposed to NGF for 5 min exhibit a 32% increase in the average barium current density. These results suggest that the effects of NGF on insulin secretion are partially mediated by an increase in calcium current through Ca channels. These results further suggest that NGF plays an important autoregulatory role in pancreatic beta-cell function. Two targets of short-term NGF-modulation are insulin secretion and calcium-channel activity.
Diabetes 2001 Aug
PMID:Nerve growth factor increases insulin secretion and barium current in pancreatic beta-cells. 1147 35

Sensory neuropathies are frequently associated with diabetes or with antimitotic treatments in humans suffering from cancer, and are in this case the most important limitation to the use of antimitotic drugs. For this reason, there is a need to establish and validate animal models of sensory neuropathies that could be routinely used, together with the already known models, for studying and evaluating the effects of putative neuroprotective compounds. In the present study, we prove by behavioral and electromyographical analyses that (a) it is possible to induce a nonlethal, exclusively sensory, reversible neuropathy by intoxicating rats with large amounts of pyridoxine, using a new schedule of intoxication; (b) 4-methylcatechol, a drug known to induce nerve growth factor synthesis, improves the clinical status of pyridoxine-intoxicated animals, shortens the duration of the disease, and restores the morphological integrity of the sensory fibers. Owing to its mode of installation and its clinical features, we propose that this model be used as an additional model for preclinical studies of neuroprotective drugs.
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PMID:Pyridoxine-induced neuropathy in rats: a sensory neuropathy that responds to 4-methylcatechol. 1149 27

Cell therapy is a promising method for treatment of hematopoietic disorders, neurodegenerative diseases, diabetes, and tissue loss due to trauma. Some of the major barriers to cell therapy have been partially addressed, including identification of cell populations, in vitro cell proliferation, and strategies for immunosuppression. An unsolved problem is recapitulation of the unique combinations of matrix, growth factor, and cell adhesion cues that distinguish each stem cell microenvironment, and that are critically important for control of progenitor cell differentiation and histogenesis. Here we describe an approach in which cells, synthetic matrix elements, and controlled-release technology are assembled and programmed, before transplantation, to mimic the chemical and physical microenvironment of developing tissue. We demonstrate this approach in animals using a transplantation system that allows control of fetal brain cell survival and differentiation by pre-assembly of neo-tissues containing cells and nerve growth factor (NGF)-releasing synthetic particles.
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PMID:Transplantation of brain cells assembled around a programmable synthetic microenvironment. 1158 58

Diabetes-induced alterations in nerve function include reductions in the retrograde axonal transport of neurotrophins. A decreased axonal accumulation of endogenous nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the vagus nerve of streptozotocin (STZ)-induced diabetic rats was previously shown. In the current study, no changes in the NGF and NT-3 protein or mRNA levels in the stomach or atrium, two vagally innervated organs, were noted after 16 or 24 weeks of diabetes. Moreover, the amounts of neurotrophin receptor (p75, TrkA, TrkC) mRNAs in the vagus nerve and vagal afferent nodose ganglion were not reduced in diabetic rats. These data suggest that neither diminished access to target-derived neurotrophins nor the loss of relevant neurotrophin receptors accounts for the diabetes-induced alteration in the retrograde axonal transport of neurotrophins. To assess whether diabetes causes a defect in axonal transport that may not be specific to neurotrophin transport, we studied the ability of a neuronal tracer (FluoroGold, FG) to be retrogradely transported by vagal neurons of control and diabetic rats. After vagal target tissue (stomach) injections of FG, the numbers of FG-labeled afferent and efferent vagal neurons were counted in the nodose ganglion and in the dorsal motor nucleus of the vagus, respectively. After 24 weeks of diabetes, FG was retrogradely transported to more than 50% fewer afferent and efferent vagal neurons in the STZ-diabetic compared to control rats. The diabetes-induced deficit in retrograde axonal transport of FG is likely to reflect alterations in basic axonal transport mechanisms in both the afferent and efferent vagus nerve that contribute to the previously observed reductions in neurotrophin transport.
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PMID:Streptozotocin-induced diabetes reduces retrograde axonal transport in the afferent and efferent vagus nerve. 1203 55

The importance of nerve growth factor (NGF) modulation of pancreatic beta cells is demonstrated by the fact that these cells secrete and respond to this trophic factor. Among NGF effects on beta cells is an increase in Na+ and Ca2+ current densities. This study investigates the mechanisms involved in the NGF-induced increase in Na+ current and the implications of this effect for insulin secretion. The following results were obtained in single beta cells cultured with NGF for 5-7 days: 1) A steady-state level of mRNA coding for type III sodium channel alpha subunit increased twofold compared with that for control cells. 2) The increase in Na+ current density was blocked either by cycloheximide or by actinomycin D, indicating that it is mediated by protein synthesis and mRNA transcription. 3) NGF treatment strengthened, by nearly fourfold, the beta-cell electrical activity; this effect is partially related to the increased Na+ current, because tetrodotoxin (TTX) decreased the duration of the depolarized plateau level. 4) Single beta cells secreted nearly two times more insulin in response to 5.6 or 15.6 mM glucose. This effect was inhibited by TTX, indicating that the enhanced Na+ current plays an important role. These data suggest that NGF could preserve an adequate expression of sodium channels and that impairment of NGF modulation could lead to deficient insulin secretion and diabetes mellitus.
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PMID:Nerve growth factor increases sodium channel expression in pancreatic beta cells: implications for insulin secretion. 1203 70

Peripheral neuropathy is a common and debilitating complication of diabetes. In animal models, neurotrophic factors can prevent progression of the neuropathy, but adverse effects prevent systemic administration in adequate doses to treat human disease. We examined whether gene transfer with replication-defective genomic herpes simplex virus (HSV) vectors modified to express nerve growth factor (NGF) could be used to prevent progression of neuropathy in mice. Diabetes induced by streptozotocin (STZ) resulted in a sensory neuropathy manifest by a decrease in the foot sensory nerve amplitude (FSA; control = 20 +/- 0.1 microV, treated = 14 +/- 0.1 microV). Transduction of dorsal root ganglia in vivo with an HSV-based vector expressing NGF under the control of the human cytomegalovirus immediate early promoter (vector SHN) or the HSV latency active promoter 2 (vector SLN) by footpad inoculation 2 weeks after STZ administration protected against the decrease in FSA (22 +/- 1.4 microV and 21 +/- 1.7 microV, respectively) measured 4 weeks later. Injection of SHN into inguinal adipose tissue 2 weeks after onset of diabetes also prevented the decrease in FSA (20 +/- 3.3 microV). These results suggest that gene transfer with an NGF-producing herpes-based vector may prove useful in the treatment of diabetic neuropathy.
Diabetes 2002 Jul
PMID:Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. 1208 54


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