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

Streptozotocin (STZ)-induced diabetes in the rat causes a significant reduction in ouabain-sensitive Na,K-ATPase pumping activity measured by 86Rb+ influx, in sciatic endoneurium (by 54%) and dorsal root ganglia (by 22%). For endoneurium, the change is similar to that of ouabain-sensitive enzymatic Na,K-ATPase activity (42%), but in dorsal root ganglia, the decrease in enzymatic Na,K-ATPase activity was much greater. 86Rb+ efflux from dorsal root ganglia showed no difference between diabetic and control animals, confirming that the abnormal 86Rb+ influx reflects Na,K-ATPase function and not abnormal membrane permeability. The significance of these findings to pathogenetic mechanisms in diabetic neuropathy is discussed.
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PMID:Rubidium (86Rb+) influx into dorsal root ganglia and sciatic nerve endoneurium of control and streptozotocin-diabetic rats: comparison with enzymatic Na,K-ATPase activity. 165 45

The effects of alpha-receptor blockade on nerve conduction, hypoxic resistance, ouabain-sensitive Na(+)-K(+)-ATPase, nerve polyols, and capillary density were examined in streptozocin-induced diabetic (STZ-D) rats. Nondiabetic and untreated diabetic control groups were used. Diabetes duration was 2 mo. There were two treated diabetic groups. A "prevention" group received 5 mg/kg prazosin for 2 mo from the induction of diabetes. A "reversal" group was untreated for the 1st mo and was given prazosin for the subsequent month. Conduction was measured in motor nerves supplying tibialis anterior and gastrocnemius muscles and sensory saphenous nerve. Diabetes resulted in 15-29% reductions in conduction velocity (P less than 0.01). In the prevention group, conduction deficits were minimal compared with untreated diabetes (P less than 0.01). In the reversal group, motor conduction was also substantially improved, although sensory conduction was not significantly affected. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for compound action potential amplitude to reach half its initial value with diabetes (P less than 0.01). This was largely prevented by prazosin treatment (P less than 0.01), although treatment had a lesser effect in the reversal group. Treatment had no effect on nerve polyol levels or Na(+)-K(+)-ATPase activity. Functional improvements with prazosin were probably based on increased vasa nervorum perfusion. There was a 20% elevation of endoneurial capillary density (P less than 0.01) in both prevention and reversal groups. We conclude that vascular factors play an important role in the etiology of experimental diabetic neuropathy, and functional changes may be corrected by chronic vasodilator treatment.
Diabetes 1991 Dec
PMID:Effects of chronic alpha-adrenergic receptor blockade on peripheral nerve conduction, hypoxic resistance, polyols, Na(+)-K(+)-ATPase activity, and vascular supply in STZ-D rats. 166 93

The pathogenesis of neuropathy and other late, degenerative complications of diabetes remains largely unresolved. Metabolic derangements thought to be responsible for their development are induced by chronic hyperglycaemia. The present studies concern as follows: sorbitol accumulation due to increased polyol pathway activity, altered myoinositol metabolism in diabetic nerve, followed by diminished sodium-potassium ATPase activity, nonenzymatic glycosylation of structural proteins and rheologic changes in microcirculation. These processes impair nerve metabolism, function and structure directly or indirectly, due to primary vascular alternations and endoneural hypoxia. Partial elucidation of the mechanism involved in pathogenesis of diabetic neuropathy has provoked emergence of new therapeutic approaches. So far their results are equivocal and require further studies. At present, improved glycaemia control is undoubtedly the most important factor in prevention and treatment of neuropathy and other late complications of diabetes.
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PMID:[Pathogenesis and treatment of diabetic neuropathy]. 166 26

The effect of streptozocin diabetes on the distribution of adrenergic and peptidergic nerves in the submucous plexus of rat ileum was investigated and compared with the changes in the myenteric plexus of the same region of ileum. There was an increase in the intensity of immunoreactivity in vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactive nerve fibers and neurons and a decrease in calcitonin gene-related peptide-like immunoreactivity but no change in substance P- and dopamine beta-hydroxylase-like immunoreactivity in the nerve fibers and neurons of the submucous plexus of both 8- and 16-wk streptozocin-diabetic rat ileum. However, in the myenteric plexus of the diabetic rat ileum, there was enlargement of varicosities and an increase followed by a slight decrease in the intensity of immunoreactivity of vasoactive intestinal polypeptide- and dopamine beta-hydroxylase-like immunoreactive nerve fibers and neurons, increased substance P-like immunoreactivity in diabetes at 16 wk, and an initial decrease (at 8 wk) followed by a recovery of calcitonin gene-related peptide-like immunoreactivity at 16 wk, but no change in neuropeptide Y-like immunoreactivity. The markedly different changes in peptidergic and adrenergic nerves between the two enteric plexuses show that diabetic neuropathy induced by streptozocin is not selective and involves factors other than neurotransmitter types.
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PMID:Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum. 169 44

This study examined the effect of treatment of control and streptozotocin-diabetic rats with a mixture of gangliosides, derived from bovine brain, on parameters of axonal transport of substance P-like immunoreactivity (SPLI) and its levels in sciatic nerve and lumbar spinal ganglia. Rats were treated daily (10 mg/kg i.p.) for 28 days and compared with untreated control and diabetic groups. The duration of diabetes was 28 days in both cases. Untreated diabetic rats showed deficits in accumulation of axonally transported SPLI proximal (59% of controls) and distal (34% of controls) to sciatic nerve ligations (left in place for 12 h). Rates of accumulation were unaltered by diabetes. There were small numerical reductions in the SPLI content of unconstricted sciatic nerve and of L4 and L5 dorsal root ganglia in diabetic rats. None of these diabetes-associated changes was altered by ganglioside treatment, nor was there any indication of an effect of gangliosides on substance P in non-diabetic rats. The implications are discussed in relation to the possible pathogenesis of diabetic neuropathy.
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PMID:Axonal transport of substance P-like immunoreactivity in ganglioside-treated diabetic rats. 169 17

Abnormalities in axonal transport have been observed in human and experimental diabetes and may be related to the pathogenesis of diabetic neuropathy. Axonal transport has previously been evaluated by indirect methods. In this study, direct-measurement techniques were applied (with computer-enhanced video-recorded images) for the first time to evaluate intra-axonal organelle speed and frequency (the amount of organelle traffic) in both the anterograde fast component (AFC) and retrograde fast component (RFC) of axonal transport in diabetic nerve. Sciatic nerve and dorsal and ventral nerve roots were studied in the animal model of insulin-dependent diabetes (BB/Wistar rat) and sciatic nerve in the non-insulin-dependent (streptozocin-induced) model of diabetes (STZ-D rat). STZ-D rats were studied at 1 mo, and BB/Wistar rats were studied at 1 and 2 mo of diabetes duration. Statistically significant decreases in peripheral axon organelle speed were found only for RFC at 1 mo of diabetes in both the BB/Wistar (8.1%) and STZ-D (5.4%) rats. The difference was no longer significant in BB/Wistar rats at 2 mo of diabetes. This recovery suggests that the underlying abnormality is reversible. No differences were seen in AFC of any axons, and the only other difference seen was a 5.1% decrement in RFC at 2 mo in the ventral roots. No significant difference was observed in any group for organelle frequencies. Other factors should be considered to explain the decrease in materials transported in accumulation studies. The transient deficits in RFC speed observed remain of undetermined significance in the pathogenesis of diabetic neuropathy.
Diabetes 1991 Jan
PMID:Amount and speed of fast axonal transport in diabetes. 170 37

Iloprost, a stable prostacyclin analog, was evaluated clinically for its ability to ameliorate the symptoms of peripheral neuropathy associated with diabetes. In an open, nonrandomized trial, 13 diabetic patients with neuropathy but without proliferative retinopathy received an intravenous infusion of Iloprost at a dose of 10 micrograms, at a rate of 0.1 micrograms/kg/h, twice daily for two weeks. The administration of Iloprost relieved the majority of such subjective symptoms as pain, numbness or sensation of cold and to a lesser extent, such autonomic symptoms as dizziness. In contrast, there was little evidence of objective improvement, e.g., in motor nerve conduction velocity. Iloprost treatment significantly inhibited the platelet aggregation rate stimulated by collagen in vitro. In the one patient tested, thermography revealed an increase in skin temperature by more than 2 degrees C. Side effects associated with Iloprost included headache (3 patients) or aggravation of pain in the extremities (2 patients) and could be ameliorated by slowing the infusion rate or by discontinuing the drug (one patient). Iloprost appears to be safe and effective for relieving the symptoms of diabetic neuropathy. Our results provide the rationale for a double-blind, clinical trial in larger populations of diabetics with peripheral neuropathy.
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PMID:Clinical efficacy of a stable prostacyclin analog, iloprost, in diabetic neuropathy. 170 9

Parotid salivary flow rates and amylase concentrations were measured in three groups of eight subjects each (normal control, non-neuropathic diabetic, and neuropathic diabetic). Flow rates were significantly reduced in neuropathic diabetic patients as compared with normal controls (p less than 0.001) and non-neuropathic diabetic patients (p less than 0.02). Amylase concentrations were similar. These data are consistent with parasympathetic denervation of the parotid gland in diabetic neuropathy and provide evidence for a widespread distribution of autonomic denervation in diabetes.
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PMID:Parotid salivary secretion in diabetic autonomic neuropathy. 171 17

Diabetic neuropathy is associated with some early defects of axonal transport in experimental animals. Axonal transport is dependent on intact microtubules, and unsubstituted lysine residues of tubulin are essential for microtubule polymerization. As lysine residues are the major target for the non-enzymatic attachment of glucose, the effect of diabetes on the extent of glycation of tubulin was investigated. There was a more than four-fold increase in the extent of glycation of tubulin in the sciatic nerve of rats with streptozotocin-induced diabetes of 2 weeks duration compared with control rats. In contrast, no such increase in glycation was observed in brain microtubule protein from diabetic rats at that stage of diabetes. Incubation of brain microtubule protein with glucose prior to in vitro polymerization showed that the early stages of glycation were not associated with inhibition of microtubule assembly. The observed glycation of peripheral nerve tubulin in early experimental diabetes may nevertheless contribute to axonal transport abnormalities through an as yet undetermined impairment of microtubule function.
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PMID:Glycation of rat sciatic nerve tubulin in experimental diabetes mellitus. 171 29

Nonenzymatic glycosylation of structural proteins and the formation of advanced glycosylation end products (AGEs) have been involved in the pathogenesis of diabetic complications. We examined the effect of aminoguanidine, a potent inhibitor of AGE formation, on functional and structural abnormalities in peripheral nerve of streptozocin-induced diabetic rats. Diabetic rats were treated with daily injections of 25 mg/kg body wt s.c. aminoguanidine (AG)-sulfate for 16 wk and compared to untreated diabetic rats. AG treatment improved motor nerve conduction velocity in 12- and 16-wk diabetic rats despite no changes in body weight, blood glucose, and HbAIc levels. AG treatment inhibited an accumulation of fluorescent AGE in diabetic nerves, and morphometric analysis of the sural nerve showed a partial effect on myelinated fiber size and axonal atrophy. These findings suggest that AG may have a beneficial effect on diabetic neuropathy and nonenzymatic glycosylation of peripheral nerve proteins.
Diabetes 1992 Jan
PMID:Effect of aminoguanidine on functional and structural abnormalities in peripheral nerve of STZ-induced diabetic rats. 172 39


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