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

Streptozotocin-induced diabetes produced marked alterations of monoamine concentrations in several hypothalamic nuclei of male and female rats. Norepinephrine (NE) concentrations were significantly elevated in the median eminence (ME), supraoptic nucleus (SON) and periventricular nucleus (PEVN) in both sexes of diabetic rats. NE concentrations in the suprachiasmatic nucleus (SCN) and ventromedial nucleus (VMN) of male and female diabetic animals remained unaltered. Serotonin (5-HT) concentrations were increased in PEVN of male and female diabetic rats. No significant changes in hypothalamic dopamine (DA) concentrations were observed. Insulin treatment reversed the diabetes-related changes in monoamine concentrations in most of the nuclei. The significance of these biochemical changes relative to the endocrine and behavioral abnormalities in diabetes is discussed.
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PMID:Diabetes-induced changes in monoamine concentrations of rat hypothalamic nuclei. 243 7

To investigate the influence of diabetes on the responsiveness of the cardiovascular system, we have examined the effects of various agents on the reactivity of the vascular smooth muscle of aortic strips obtained from age-matched control and diabetic rats. Norepinephrine (NE) contracted the aortic strips obtained from age-matched control and diabetic rats in a concentration-dependent manner, but maximal contraction of aortic strips in response to NE was enhanced in diabetic rats. The EC50 value for NE in the diabetic aortic strips was similar to that in the aorta from age-matched controls. Ca-induced contracture of the aortic strips which were depolarized with isotonic K+ (60 mM) was potentiated in aortic strips from diabetic rats, when compared with those from age-matched controls. Ca-induced contracture of aortic strips, preincubated with 10(-6) M NE and 10(-6) M nicardipine in Ca2+-free Krebs-Henseleit solution (KHS), was not significantly different in age-matched control and diabetic rats. Bay K 8644, an activator of calcium channels, produced an increase in the force of contraction of the slightly depolarized aorta from diabetic rats. Phasic contraction induced by phenylephrine (PE) in the presence of 10(-6) M nicardipine in Ca2+-free KHS was significantly enhanced in aortic strips obtained from diabetic rats. These results demonstrate that NE-induced contraction of the aortic strips obtained from diabetic rats was significantly enhanced, and that this increased contractile response of the aorta to NE may be due to an increased influx of extracellular calcium through the voltage-dependent Ca2+ channels, but not through the receptor-operated Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of increased responses of the aorta to alpha-adrenoceptor agonists in streptozotocin-induced diabetic rats. 246 83

1. The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2. Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3. Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with alpha-methyl-p-tyrosine. Turnover was found to be increased in all three tissues. 4. The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5. It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na+, K+-ATPase depression.
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PMID:Tissue noradrenaline and the polyol pathway in experimentally diabetic rats. 250 23

Noradrenaline levels in the superior cervical ganglion and sciatic nerve were significantly reduced in chronic streptozotocin-induced diabetes in rats. Sciatic nerve sheath in vitro biosynthesis of 6-keto prostaglandin F1 alpha (6KPGF1 alpha; the stable metabolite of prostacyclin) was significantly reduced but not in acute experimental diabetes. Nerves with reduced 6KPGF1 alpha had an excessive response to arachidonic acid stimulation. We suggest that the reduced endogenous biosynthesis of prostacyclin is due to reduced substrate availability, possibly due to the reduced noradrenaline. The implications of these findings on the pathogenesis of diabetic neuropathy are discussed. Neuropathy was found to involve all fibre populations studied (motor, sensory and sympathetic) and progressed with duration of diabetes.
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PMID:Prostacyclin and noradrenaline in peripheral nerve of chronic experimental diabetes in rats. 252 6

Retention of one-trial passive avoidance training was compared in diabetic and nondiabetic rats. Also compared were corticosterone concentrations associated with both training and retention testing, catecholamine excretion related to training, and regional brain catecholamine concentrations accompanying retention testing. Diabetic rats showed significantly better retention for the task than did nondiabetic rats. Associated with retention differences, diabetic rats had higher epinephrine excretion and nondiabetic rats had lower excretion after footshock training relative to baseline measures. Norepinephrine excretion was elevated in diabetics both in baseline measurement and during the 24 hr following footshock training. No differences were found in baseline or stimulated corticosterone concentration between diabetic and nondiabetic rats. Diabetic rats had higher concentrations of norepinephrine (NE) and dopamine (DA) and lower 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in hypothalamus and higher NE in brain stem and amygdala than did nondiabetics, although both diabetic and nondiabetic rats had reduced DA and NE following retention testing. The results indicate that there are biochemical alterations in diabetes that may have important behavioral impact.
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PMID:Stress and behavior in streptozotocin diabetic rats: biochemical correlates of passive avoidance learning. 252 5

The effects of streptozotocin-induced (STZ) diabetes on neuroendocrine and sexual function were evaluated in adult male rats. Adult male rats were injected with STZ (50 mg/kg) or vehicle and tested for copulatory behavior 7, 14, and 21 days later. The rats were killed 1 month after STZ or vehicle treatment for measurement of plasma hormone levels, hypothalamic catecholamine turnover, LHRH content, and in vitro pituitary function. The STZ rats showed significant deficits in mount, intromission, and ejaculatory behaviors. Plasma levels of testosterone, LH, FSH, and PRL were all significantly reduced in the STZ compared to the control rats, but in vitro LH secretion was enhanced after STZ treatment. In vitro PRL secretion and the inhibitory response to dopamine did not differ between the two groups. The levels of LHRH were reduced in the medial basal hypothalamus (MBH), but LHRH levels in the median eminence (ME) and anterior hypothalamus (AH) were unchanged after STZ treatment. Norepinephrine turnover was reduced in the ME, MBH, and AH of the STZ rats, while dopamine turnover was unchanged in the ME, increased in the MBH, and reduced in the AH of the STZ rats compared to those in the vehicle-treated controls. These results suggest that changes in pituitary and testicular function in rats made diabetic by STZ treatment are secondary to changes in hypothalamic catecholamine metabolism. Changes in copulatory behavior could be due to both reductions in plasma testosterone levels as well as changes in central neurotransmitter metabolism.
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PMID:Streptozotocin-induced deficits in sex behavior and neuroendocrine function in male rats. 252 88

The influence of alloxan-induced diabetes on the adrenergic constriction of the rat cerebral vasculature was investigated in the in situ perfused brain preparation. The preparation was perfused with an artificial medium at a constant flow rate and the change in perfusion pressure was measured. Norepinephrine (NE) and serotonin produced a dose-dependent increase in the perfusion pressure, but only the effect of NE was significantly enhanced in the diabetic rats. Such an enhancement of NE-induced vasoconstriction was not observed in the perfused hindquarter preparations from the diabetic rats. Propranolol (1 microM) potentiated the cerebrovascular constriction by NE and abolished the difference between diabetic and control rats at low doses of NE. However, vasoconstriction by the higher doses of NE in the diabetic rats was still enhanced even in the presence of propranolol. The cerebrovascular constriction by phenylephrine was also enhanced in the diabetic rats, while the vasoconstricting effects of clonidine, xylazine and oxymetazoline were not affected by diabetes. These results suggest that the enhanced cerebrovascular constriction by NE may be due to either the reduced response through beta-adrenoceptors or the enhanced response through alpha 1-adrenoceptors. The enhanced adrenergic constriction of the cerebral vasculature might be concerned with the high incidence of neurological deficit in stroke patients with diabetes.
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PMID:Enhanced adrenergic response of the cerebral vasculature in alloxan-induced diabetic rats. 263 66

The etiology of autonomic neuropathy in insulin-dependent diabetes mellitus (IDDM) is unknown. Previous studies have noted the presence of anti-adrenal medullary antibodies in IDDM. Recently, we have also demonstrated the presence of anti-sympathetic ganglia antibodies in IDDM. We initiated a study to evaluate whether subjects with complement-fixing anti-adrenal medullary (CF-ADM) and anti-sympathetic ganglia (CF-SG) antibodies have a decreased catecholamine response to change in posture. Seven IDDM subjects aged 19-41 yr with duration of disease 5-21 yr at the time of the posture study were evaluated. Serums collected longitudinally were evaluated for the presence of CF-ADM and CF-SG antibodies. Three IDDM subjects were CF-ADM- and CF-SG- at all testing intervals (Ab- group). Four IDDM subjects were CF-ADM+ and/or CF-SG+ on at least one testing date (Ab+ group). Baseline mean norepinephrine and epinephrine levels were not significantly different in Ab+ and Ab- subjects. Norepinephrine levels 5 min after standing were mean +/- SD 227 +/- 16 and 419 +/- 48 pg/ml for Ab+ and Ab- subjects, respectively (P less than .03). The means of the 5-min minus basal norepinephrine levels were 88 +/- 42 (Ab+) and 207 +/- 26 (Ab-) pg/ml (P less than .03). Mean epinephrine levels after 5 min of standing were 35 +/- 16 (Ab+) and 101 +/- 44 (Ab-) pg/ml (P less than .03). The means of the 5-min minus basal epinephrine levels were 1 +/- 5 (Ab+) and 43 +/- 38 (Ab-) pg/ml (P less than .03).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jul
PMID:Anti-sympathetic nervous system autoantibodies. Diminished catecholamines with orthostasis. 273 66

Recent studies in man demonstrated a marked ketogenic effect of increased plasma norepinephrine concentrations as observed in diabetic ketoacidosis. Since this effect may have been due either to increased substrate supply for ketogenesis (lipolysis) or to direct hepatic activation of ketogenesis, the latter mechanism was examined in isolated rat hepatocytes. Incubation of hepatocytes with norepinephrine (10(-7) to 10(-4) M) resulted in a dose-dependent increase in conversion of the long-chain fatty acid [1-14C]palmitate into ketone bodies and CO2. Norepinephrine decreased [1-14C]palmitate conversion into triglycerides without affecting fatty acid uptake. Norepinephrine enhanced ketogenesis from [1-14C]palmitate in a physiologic range of fatty acid concentrations (0.5-2.5 mM), but failed to affect fatty acid esterification to phospholipids or mono- and diglycerides. In contrast to long-chain fatty acids, oxidation of the medium-chain fatty acid [1-14C]octanoate to ketone bodies was not enhanced by norepinephrine, whereas CO2 production increased. The effect of norepinephrine on [1-14C]fatty acid oxidation was blocked by the alpha 1 receptor blocker prazosin. The results demonstrate that norepinephrine diverts long-chain fatty acids into the pathways of oxidation and ketogenesis away from esterification, suggesting enhanced carnitine-dependent mitochondrial fatty acid uptake. The studies using octanoate indicated that norepinephrine also enhanced fatty acid oxidation by increasing the flux of acetyl-CoA through the Krebs cycle. The data suggest that stress-associated sympathetic activation and norepinephrine discharge, as observed in diabetic ketoacidosis, result in direct activation of ketogenesis in the liver.
Diabetes 1985 Aug
PMID:Effect of norepinephrine on ketogenesis, fatty acid oxidation, and esterification in isolated rat hepatocytes. 286 86

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10-12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes. 286 46


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