Biomedical subjects

N E Cameron

Publications and source records attributed to N E Cameron.

At least 73 records · Page 4Linked to original sources

PubMed1993

Rapid reversal of a motor nerve conduction deficit in streptozotocin-diabetic rats by the angiotensin converting enzyme inhibitor lisinopril.

The effect of treatment of rats with the angiotensin converting enzyme inhibitor lisinopril after 5 weeks of untreated streptozotocin-diabetes was examined by daily monitoring of sciatic motor conduction velocity to tibialis anterior muscle. Diabetes produced a 31.5% decrease in conduction velocity (P < 0.001). Lisinopril treatment caused a progressive improvement which was significant after 3 days (P = 0.002), full normalization being achieved by 6 days (P < 0.0001). After 7 days of treatment there followed a 7-day washout period in which no lisinopril was given. During this time conduction velocity declined to untreated diabetic levels over 3 days. A subsequent treatment period resulted in complete normalization of conduction velocity within 2 days (P < 0.0001). Thus, the marked functional effects seen for vasodilator treatment with lisinopril suggest that angiotension converting enzyme inhibitors may have potential therapeutic value in the treatment of diabetic neuropathy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Pharmacological manipulation of vascular endothelium function in non-diabetic and streptozotocin-diabetic rats: effects on nerve conduction, hypoxic resistance and endoneurial capillarization.

We examined the potential for some of the abnormalities of vascular endothelium found in diabetes mellitus to cause neuropathic changes. Non-diabetic rats were treated for 2 months with the cyclo-oxygenase inhibitor flurbiprofen (5 mg.kg-1.day-1) to reduce prostacyclin production, the nitric oxide synthase inhibitor NG-nitro-L-arginine (5 or 25 mg.kg-1.day-1), or combined treatment. There were dose-dependent reductions in sciatic motor and saphenous sensory conduction velocity. The two inhibitors acted synergistically, thus, the 5-6% motor conduction deficits (p < 0.01) produced by either flurbiprofen or NG-nitro-L-arginine (5 mg.kg-1.day-1) increased to 17% (p < 0.001) for combined treatment. With NG-nitro-L-arginine (25 mg.kg-1.day-1) and flurbiprofen, motor and sensory conduction velocity were reduced by 23% (p < 0.001) and 12% (p < 0.001), respectively, matching the deficits following 2-month streptozotocin diabetes. NG-nitro-L-arginine (25 mg.kg-1.day-1) and flurbiprofen together produced a 13% prolongation of the time taken for 80% hypoxic conduction failure in vitro (p < 0.05) and a 10% reduction in sciatic capillary density. A second investigation tested an alternative hypothesis that overproduction of nitric oxide was responsible for vascular-related complications in diabetes, the prediction being that NG-nitro-L-arginine (5 mg.kg-1.day-1) would prevent nerve dysfunction. However, rather than prophylaxis during 2-month streptozotocin diabetes, treatment exacerbated nerve abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

The effects of evening primrose oil on nerve function and capillarization in streptozotocin-diabetic rats: modulation by the cyclo-oxygenase inhibitor flurbiprofen.

1. The aims of this study were first, to examine whether deficits in nerve conduction in streptozotocin-diabetic rats could be reversed by a 10% dietary supplement of evening primrose oil. Second, to determine the time-course of reversal, and third, to assess whether the effects could be blocked by the cyclo-oxygenase inhibitor flurbiprofen (5 mg kg-1 day-1). 2. One-month diabetes produced 20% and 15% deficits in sciatic motor and saphenous sensory conduction velocity respectively, which were maintained over 2 months diabetes. 3. The effect of 1-month evening primrose oil treatment on abnormalities caused by an initial month of untreated diabetes was examined. Motor and sensory nerve conduction velocity were restored to the non-diabetic level. 4. Resistance to hypoxic conduction failure was investigated for sciatic nerve trunk in vitro. The 80% conduction failure times were 29% and 55% prolonged by 1- and 2-month diabetes respectively. Evening primrose oil did not reverse the increased hypoxic resistance following 1-month untreated diabetes. 5. Sciatic nerve endoneurial capillary density was not significantly affected by diabetes, but was 16% increased in diabetic rats with reversal by evening primrose oil treatment for 1 month compared to 2-month untreated diabetes. 6. Serial motor conduction velocity measurement after 3-month untreated diabetes revealed complete normalization by evening primrose oil within 4 days. Cessation of treatment resulted in a rapid decline in conduction velocity over 24 h. 7. In a preventive study of 2-month duration, 6 groups of rats were used. These comprised non-diabetic controls, diabetic rats, and evening primrose oil-treated diabetic rats, both with and without flurbiprofen treatment. Flurbiprofen had no significant effect in non-diabetic rats, but produced an 11% worsening of motor conduction velocity and a 21% reduction of sciatic capillary density in diabetic rats. Evening primrose oil prevented the decreases in conduction velocity and increased hypoxic resistance with diabetes, and caused a 23% increase in capillary density. Flurbiprofen completely blocked the effect of evening primrose oil on conduction velocity, resistance to hypoxia, and capillarization.8. Six main conclusions were reached. First, evening primrose oil rapidly reverses conduction deficits in diabetic rats. Second, the effects of treatment may be very short-lived, suggesting a primary metabolic action. Third, evening primrose oil cannot reverse established changes in hypoxic resistance over 1-month treatment. Fourth, long-term treatment causes angiogenesis, suggesting a vascular action. Fifth,products of cyclo-oxygenase-mediated metabolism are necessary for maintaining vasa nervorum integrity in diabetic rats. Sixth, evening primrose oil probably acts by providing substrate for vasodilator prostanoid synthesis by vasa nervorum.

Action Potentials↗

PubMed1993

Polyol pathway-related skeletal muscle contractile and morphological abnormalities in diabetic rats.

This study examined the effect of inhibition of aldose reductase, the first enzyme in the polyol pathway, on fast and slow twitch skeletal muscle morphology and function in streptozotocin-induced diabetes in rats. There was a preventative investigation with diabetes duration of 4 months, and a reversal investigation where treatment was given for 2 months following an untreated period of 2 months. For slow twitch soleus muscle, contractions were prolonged by diabetes, and this was partially prevented but not reversed by treatment. Relaxation was profoundly slowed, and both prevention and reversal ameliorated the changes. Diabetes had minimal effects on tension production for soleus. However, for fast twitch extensor digitorum longus, although there was little effect on speed-related contractile parameters, tetanic tension production was progressively reduced with diabetes duration. This effect was antagonized by treatment. Soleus fatigue resistance was markedly reduced by diabetes, but restored to normal by treatment. There was a reduction in oxidative enzyme staining (succinic dehydrogenase), and capillary-fibre ratio, both of which were ameliorated by aldose reductase inhibition. Mean soleus fibre area was reduced after 4 months of diabetes, and this was prevented but not reversed by treatment. Fibre area was also reduced in extensor digitorum longus, particularly for fast glycolytic fibres. There was a small amelioration with treatment. It is concluded that enhanced polyol pathway activity makes a contribution to diabetic myopathy, and that aldose reductase inhibitors can prevent this by actions on muscle fibres and their vascular supply.

Aldehyde Reductase↗

PubMed1993

Nerve function in experimental diabetes in rats: effects of electrical stimulation.

The effects of unilateral electrical stimulation of the peroneal sciatic nerve branch were studied in streptozocin-diabetic rats of 12-wk duration. Stimulation was carried out over 7 days (10 Hz, 8 h/day) with chronically implanted electrodes. Compared with controls, there was a 25% conduction velocity (CV) deficit for the peroneal nerve supplying tibialis anterior muscle in the unstimulated leg, which was corrected by stimulation. For tibial fibers supplying soleus muscle, a similar diabetic CV deficit (20%) was normalized by stimulation, although soleus axons were not directly activated. In saphenous nerve, which has a functionally separate vascular supply, peroneal stimulation was ineffective. In anesthetized diabetic rats, stimulation caused an 18% reduction in tibialis anterior CV after 4 h. However, serial measurements showed progressive normalization of CV over 4 days of stimulation. On termination, CV returned to diabetic levels over 36-60 h. Sciatic nerve showed a 70% increase in resistance to hypoxic conduction failure with diabetes, which was halved by chronic stimulation. Acute experiments demonstrated that peroneal stimulation increased sciatic vascular conductance by 60%. We conclude that stimulation causes activity-related improvements in diabetic nerve blood flow and metabolism.

Animals↗

PubMed1992

Angiotensin converting enzyme inhibition prevents development of muscle and nerve dysfunction and stimulates angiogenesis in streptozotocin-diabetic rats.

The effects of the angiotensin converting enzyme inhibitor lisinopril on slow and fast twitch muscle contractile properties, nerve conduction and hypoxic resistance, and muscle and nerve capillary density were examined in streptozotocin-diabetic rats. Prolongation of soleus contraction and relaxation were partially prevented by treatment (p less than 0.01). A 22% deficit in fast twitch extensor digitorum longus tetanic tension production was also ameliorated (p less than 0.01). Sciatic motor and sensory conduction velocity, 25% and 12% reduced by diabetes respectively, were 75% normalized by lisinopril (p less than 0.01). There was a 47% increase in resistance to hypoxic conduction block with diabetes (p less than 0.01). Lisinopril treatment resulted in normal hypoxic resistance. Capillarization of nerve and muscle was little affected by diabetes; however, there was a 17% increase in capillary density in sciatic nerve, and a 40% increase in extensor digitorum longus muscle with lisinopril (p less than 0.01). For soleus, a smaller treatment-induced increase in capillary density led to an elevated capillary/muscle fibre ratio (p less than 0.01). These results suggest that lisinopril promoted angiogenesis. It was concluded that the beneficial effect of preventive lisinopril treatment is likely to depend upon a reduction of peripheral vascular resistance and improvement of tissue blood flow, which implicates relative hypoxia as an important factor in the development of myopathy and neuropathy in experimental diabetes.

Action Potentials↗

PubMed1992

The effect of the calcium antagonist nifedipine on peripheral nerve function in streptozotocin-diabetic rats.

Recent data suggests that reduced nerve blood flow is implicated in the aetiology of experimental diabetic neuropathy, which may be prevented by manipulations that reduce receptor-mediated vasoconstrictor activity. This investigation examines the effects of nifedipine, a voltage-sensitive calcium channel antagonist which has a direct vasodilatory effect on vessels, on nerve conduction, hypoxic resistance and capillary density in streptozotocin-induced diabetic rats. Treated and non-treated non-diabetic and diabetic groups were employed. Diabetes duration was 2 months. Treatment was preventive, groups received a nifedipine dietary supplement (40 mg.kg-1.day-1) for 2 months from the start of the study. Conduction was measured in sciatic motor branches supplying tibialis anterior and gastrocnemius muscles, and sensory saphenous nerve. Diabetes resulted in a 23-28% reduction in motor conduction velocity (p < 0.001), and a 15% deficit for sensory saphenous nerve (p < 0.001). In the nifedipine-treated diabetic group, motor and sensory conduction deficits were minimal compared with non-treated diabetes (p < 0.001). Nifedipine treatment had no significant effect on conduction velocity in non-diabetic rats. In vitro measurement of sciatic nerve hypoxic resistance revealed a 60% increase in the time taken for compound action potential amplitude to reach half its initial value with diabetes (p < 0.001). This was not significantly affected by nifedipine treatment. Experimental diabetes or nifedipine treatment did not significantly alter sciatic nerve endoneurial capillary density. We conclude that nifedipine, a vasodilator which acts directly on vascular smooth muscle, prevents nerve conduction deficits in experimental diabetes.

Action Potentials↗

PubMed1992

Effects of aminoguanidine on peripheral nerve function and polyol pathway metabolites in streptozotocin-diabetic rats.

The effect of 2 months aminoguanidine treatment on nerve conduction abnormalities was studied in streptozotocin-diabetic rats. Treatment with aminoguanidine from the induction of diabetes mellitus prevented a 22% decrease in sciatic motor nerve conduction velocity (p less than 0.001), and a 10% deficit in sensory saphenous conduction velocity (p less than 0.01). There was a 49% increase in resistance of sciatic nerve to hypoxic conduction failure in vitro. This was not significantly affected by aminoguanidine treatment. Sciatic nerve polyol pathway metabolites, sorbitol and fructose, were elevated 10-fold by diabetes (p less than 0.001). Myo-inositol levels were 18% decreased by diabetes. Aminoguanidine treatment had no significant effect on sorbitol, fructose or myo-inositol levels. Aminoguanidine has been identified as both an inhibitor of the formation of advanced glycation end products, and an aldose reductase inhibitor. The data suggest that beneficial actions on nerve function do not depend on the latter property. They support the notion that advanced glycation end products contribute to the aetiology of early diabetic neuropathy, possibly acting via a vascular mechanism, and that aminoguanidine treatment may have therapeutic applications.

Animals↗

PubMed1992

Impaired contraction and relaxation in aorta from streptozotocin-diabetic rats: role of polyol pathway.

The effects of 3 months streptozotocin-induced diabetes mellitus on contraction and relaxation of aorta were examined in vitro. A further diabetic group was treated with a novel sulphonylnitromethane-based aldose reductase inhibitor for 3 months following diabetes induction. Diabetes resulted in reduced maximal tension production, particularly for responses to phenylephrine (p < 0.001) and serotonin (p < 0.001). However, with aldose reductase inhibitor treatment, responses were in the non-diabetic range. The ratio of maximum contractions to noradrenaline and phenylephrine were 28% elevated by diabetes (p < 0.01), which may suggest increased alpha 2-adrenoreceptor-mediated responses. Endothelium-independent relaxation to glyceryl trinitrate was unaffected by diabetes or treatment. By contrast, there were 38% deficits in endothelium-dependent relaxation to acetylcholine (p < 0.001) and Ca2+ ionophore A23187 (p < 0.001) with diabetes which were prevented by aldose reductase inhibitor treatment (p < 0.001). A 121% shift in the concentration giving a 50% maximum effect for acetylcholine towards lower sensitivity with diabetes (p < 0.001) was also largely corrected by treatment (p < 0.001). A non-diabetic group treated with aldose reductase inhibitor showed a 30% decrease in the 50% effective concentration for acetylcholine (p < 0.05). A 15% deficit in maximum relaxation to the ATP-sensitive K+ channel opener cromakalim for the diabetic group (p < 0.001) was prevented by aldose reductase inhibitor treatment (p < 0.01). We conclude that there are polyol pathway related abnormalities for contraction, some aspects of endothelium-independent relaxation, but particularly for endothelium-dependent relaxation in aorta from chronic streptozotocin-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampholyte Mixtures↗

PubMed1992

Dissociation between biochemical and functional effects of the aldose reductase inhibitor, ponalrestat, on peripheral nerve in diabetic rats.

1. The aim of the study was to examine the effects in rats of two different doses of the aldose reductase inhibitor, ponalrestat, on functional measures of nerve conduction and sciatic nerve biochemistry. 2. After 1 month, streptozotocin-induced diabetes produced 22%, 23% and 15% deficits in conduction velocity of sciatic nerves supplying gastrocnemius and tibialis anterior muscles and saphenous sensory nerve respectively compared to controls. These deficits were maintained over 2 months diabetes. 3. Slower-conducting motor fibres supplying the interosseus muscles of the foot did not show a diabetic deficit compared to onset controls, however, there was a 13% reduction in conduction velocity after 2 months diabetes relative to age-matched controls, indicating a maturation deficit. 4. Resistance to hypoxic conduction failure was investigated for sciatic nerve trunks in vitro. There was an increase in the duration of hypoxia necessary for an 80% reduction in compound action potential amplitude with diabetes. This was progressive; after 1 month, hypoxia time was increased by 22% and after 2 months by 57%. 5. The effect of 1-month treatment with the aldose reductase inhibitor, ponalrestat, on the abnormalities caused by an initial month of untreated diabetes was examined. Two doses of ponalrestat were employed, 8 mg kg-1 day-1 (which is equivalent to, or greater than, the blockade employed in clinical trials), and 100 mg kg-1 day-1. 6. Sciatic nerve sorbitol content was increased 7 fold by diabetes. Both doses were effective in reducing this; 70% for 8 mg kg-1 day-1, and to within the control range for 100 mg kg-1 day-1.

Aldehyde Reductase↗

PubMed1992

Muscle and nerve dysfunction in rats with experimental galactosaemia.

The effects of up to 4 months dietary supplementation with 40% galactose on muscle and nerve function were examined in rats. Galactitol, a polyol pathway metabolite, accumulated to high levels in both tissues. This led to changes similar to those found in experimental diabetes, which were largely prevented by treatment with an inhibitor of the first enzyme in the pathway, aldose reductase. For fast twitch extensor digitorum longus muscle there was weight loss, fibre damage, slowing of twitch time to peak, increased twitch tension, and reduced tetanic tension. There were no relaxation deficits. For slow twitch soleus there were no changes in tension production. However, contraction and relaxation for both twitch and tetanus were prolonged. Fatigue resistance was reduced after 1 week. Damage in soleus led to a reduction in mean fibre area after 2 months, which largely recovered by 4 months. There was a selective loss of fast oxidative glycolytic fibres. Histochemical staining for succinic dehydrogenase was normal in galactosaemic soleus, in contrast to the marked reduction seen in diabetes. Sciatic nerve conduction velocity was reduced after 2 months, particularly in normally fast conducting motor and sensory fibres. Resistance to hypoxic conduction block was increased in galactosaemic nerves to diabetic levels. It was concluded that polyol pathway hyperactivity is likely to contribute to the aetiology of diabetic myopathy and neuropathy, and that experimental galactosaemia provides a good model in which to study pathway effects without the complicated hormonal changes found in diabetes.

Adenosine Triphosphatases↗

PubMed1992

Effects of lengthened immobilization on functional and histochemical properties of rabbit tibialis anterior muscle.

The imposition of long-term lengthened immobilization on rabbit tibialis anterior (TA) muscles resulted in rapid increases in slow oxidative (SO) fibre number. After 2 weeks, SO number had increased 2-fold and was 5 times greater after 6 weeks immobilization. There were also fibre-type-specific effects on SO, fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibre areas. Twitch strength was unchanged throughout immobilization whilst production of tetanic tension was impaired during the initial period but had returned to control levels by 6 weeks. Twitch contraction times and isometrically determined rates of rise and relaxation were largely unaffected by immobilization despite the marked increase in expression of slow myosin. The change in phenotypic expression of the lengthened TA was not attributable to chronically increased levels of activation since integrated EMG activity was unchanged from control values throughout the immobilization period. Thus it is suggested that a chronic increase in tension consequent on the lengthening procedure is a potent stimulus for fast-to-slow myosin transformation.

Analysis of Variance↗

PubMed1992

Polyol pathway-mediated changes in cardiac muscle contractile properties: studies in streptozotocin-diabetic and galactose-fed rats.

Contractile properties of left ventricular papillary muscles and atria from streptozotocin-diabetic and from non-diabetic rats fed a 40% galactose diet were measured in vitro. There was a characteristic slowing of twitch responses for both tissues and both treatments (P < 0.05). Time to peak contraction was prolonged by 18-33% and maximum rate of contraction was reduced by 10-17%. Relaxation was also affected, with a 13-37% increase in half-relaxation time and a 7-25% reduction in the maximum rate of relaxation. There were treatment differences between papillary muscles and left atrium, diabetes having a more marked effect on the former, whereas galactosaemia caused more pronounced changes in the latter. The resting beat rate of the right atrium was 22% reduced in diabetic and galactosaemic rats (P < 0.01). When maximally stimulated with isoprenaline, beat rate did not rise to the level of stimulated controls (P < 0.01). Papillary muscle speed-related contractile properties also showed a reduced response to isoprenaline in diabetic and galactosaemic groups compared to normal controls. The greatest deficit was found for maximum rate of relaxation where responsiveness was 41 and 34% less for diabetic and galactosaemic groups respectively (P < 0.01). Polyol pathway metabolites in diabetic ventricles were increased 8-fold. In galactosaemic rats galactitol accumulation led to a 530-fold increase in polyols. The data suggest that polyol pathway activity may be an important factor in the aetiology of contractile and chronotropic changes in diabetic and galactosaemic cardiomyopathy.

Animals↗

PubMed1991

Chronic stimulation accelerates functional recovery of immobilized soleus muscles of the rabbit.

Unilateral immobilization of rabbit hindlimbs was carried out for 2 weeks with an ankle angle of 90 deg. This was followed either by natural recovery for a further 2 or 4 weeks, or by chronic electrical stimulation of the soleus nerve during 2 weeks recovery using a low-frequency pattern of activation. Immobilization caused gross degeneration and functional disruption of soleus. Mean fibre area was reduced by 60% compared with unoperated controls, twitch and tetanic tensions by 90% and there was speeding of the rising phase of contraction. Natural recovery for 2 weeks had little effect; some regeneration occurred but muscle fibres remained atrophied and immature as indicated by the histochemical expression of both fast and slow myosin. Function continued to be grossly impaired, twitch and tetanic tensions were 66 and 79% reduced and the time-to-peak twitch tension 31% faster than controls. Prolonging the natural recovery period to 4 weeks increased muscle fibre area to 60% of normal, and increased the acquisition of mature staining properties but most functional characteristics remained impaired. Stimulated muscles had normal fibre areas, mature appearance and functional improvements which matched and in most cases exceeded those seen after natural recovery for 4 weeks. Thus chronic low-frequency stimulation of soleus muscles accelerates recovery of structure and function following degenerative immobilization atrophy and may represent an important therapeutic aid in patient rehabilitation.

Animals↗

PubMed1991

Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits.

A reduction in nerve blood flow in chronic experimental diabetes has been linked to impaired conduction. Recently, there have been reports that this is preceded by a period of functional hyperemia. The present investigation explored early changes in sciatic nerve endoneurial blood flow and function in streptozocin-treated rats with durations of diabetes from 1 wk to 4 mo. Blood flow was monitored by microelectrode polarography and hydrogen clearance in thiobutabarbital (Inactin)-anesthetized animals. It was reduced by 41% as early as 1 wk after diabetes induction. There was no evidence of an early functional hyperemia, flow remaining 44% depressed up to 4 mo. In another investigation, similar reductions in blood flow were acutely induced in normal rats rendered hyperglycemic by glucose infusion. In diabetic animals, conduction velocity in sciatic branches supplying gastrocnemius and tibialis anterior muscles was correlated with blood flow. The link was further tested using a group of 2-mo diabetic rats treated with guanethidine. Treatment caused a functional adrenergic sympathectomy, and blood flow increased to within the normal range. Conduction velocity, depressed by 26% with diabetes, was normalized by treatment. These observations support the hypothesis that hyperglycemia-induced blood flow reductions and resultant endoneurial hypoxia are important factors underlying nerve conduction deficits early in the development of diabetic neuropathy.

Animals↗

PubMed1991

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.

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.

Action Potentials↗

PubMed1991

Essential fatty acid diet supplementation. Effects on peripheral nerve and skeletal muscle function and capillarization in streptozocin-induced diabetic rats.

Effects of essential fatty acids on nerve conduction, hypoxic resistance, skeletal muscle contractile properties, and capillary density were examined in streptozocin-induced diabetic rats. Nondiabetic and diabetic controls and three diabetic groups treated with 10% supplements of corn oil, evening primrose oil (Efamol), or a mixture of 80% evening primrose oil and 20% fish oil (Efamol Marine) for 2 mo were used. Efamol and Efamol Marine increased plasma gamma-linolenic acid levels, but arachidonic acid was elevated only with Efamol. Diabetes resulted in 15-29% reductions in sciatic motor and sensory saphenous nerve conduction velocity. Efamol prevented conduction deficits more effectively than Efamol Marine, and corn oil had no effect. In vitro measurement of sciatic nerve hypoxic resistance revealed a 49% increase in the time taken for action potential amplitude to decline by 50% with diabetes. Corn oil had no significant effect. With Efamol, hypoxic resistance was within the nondiabetic range. Efamol Marine produced intermediate results. Functional improvements may relate to enhanced vasa nervorum perfusion, because endoneurial capillary density increased by 22% with Efamol, angiogenesis perhaps resulting from eicosanoid production from arachidonic acid. Soleus muscle contractions were prolonged by diabetes. This was partially corrected by treatment, Efamol being most effective. Extensor digitorum longus muscle had reduced tetanic tension with diabetes, and this was prevented by all treatments. Soleus showed a modest increase in capillarization with Efamol, which may have contributed to reduced susceptibility to fatigue. The data suggest involvement of abnormal fatty acid metabolism in the etiology of diabetic neuropathy and myopathy.

Animals↗

PubMed1990

Changes in skeletal muscle contractile properties in streptozocin-induced diabetic rats and role of polyol pathway and hypoinsulinemia.

Functional changes in slow-twitch soleus and fast-twitch extensor digitorum longus muscles were assessed after 2 mo of streptozocin-induced diabetes in rats. For soleus, there was a slowing of twitch times both for contraction and relaxation and a reduction of maximum tetanic relaxation rate. There was little effect on strength performance assessed by maximal tetanic tension production. Treatment with the aldose reductase inhibitor ponalrestat largely prevented relaxation defects but had little effect on contraction. For the fast muscle, twitch times were relatively unaffected, but maximum tetanic relaxation rate was reduced. In addition, tetanic tension output decreased. These changes were largely prevented by ponalrestat treatment. The effects of partial insulin therapy were also investigated. This regimen reduced hypoinsulinemia, but sufficient hyperglycemia remained to stimulate the polyol pathway. It prevented the slowing of soleus twitch contraction but had no effect on relaxation. For extensor digitorum longus, insulin produced further deleterious effects on tetanic tension and maximum relaxation rate, which were antagonized by ponalrestat. A 1% dietary myo-inositol supplement had little effect on contractile function in slow or fast muscles. It was concluded that polyol-pathway activity is an important factor underlying skeletal muscle functional changes in diabetes, probably acting through disruption of Ca2+ handling. Hypoinsulinemia was considered a secondary factor causing atrophy, particularly of fast muscles. There was no evidence of effects dependent on neuropathy.

Aldehyde Reductase↗