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

1. Injection of L-tryptophan (750 mg/kg body wt.) led to pronounced hypoglycaemia in fed and 48 h-starved rats. 2. The hypoglycaemic effect is blocked by pretreament with p-chlorophenylalanine, compound MK-486 [Carbidopa: L-alpha-(3,4-dihydroxybenzyl)-alpha-hydrazinopropionic acid monohydrate] or methysergide, and potentiated by pargyline. 3. 5-Hydroxy-L-tryptophan is more potent and induces a more rapid hypoglycaemia than does tryptophan. Other tryptophan metabolites were not associated with hypoglycaemia. 4. Adrenalectomy increases, and acute experimental diabetes strongly decreases, the sensitivity of rats to tryptophan induction of hypoglycaemia. Diabetic animals were also insensitive to 5-hydroxytryptophan. 5. Metabolite concentration changes in the livers from tryptophan-treated 48h-starved and diabetic animals were consistent with a rapid inhibition of gluconeogenesis. This did not correlate with the hypoglycaemic response. 6. Tryptophan treatment was associated with a significant increase in the plasma [beta-hydroxybutyrate]/[acetoacetate] ratio; there were no changes in the plasma concentrations of urea, triacyglycerol, non-esterified fatty acids and glycerol. 7. These observations suggest that the hypoglycaemic action of tryptophan is mediated through formation of intracellular 5-hydroxytryptamine, and is unrelated to the inhibition of gluconeogenesis. It is unlikely that this increased synthesis of 5-hydroxytryptamine involves directly either the adrenal glands or the central nervous system.
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PMID:Tryptophan and the control of plasma glucose concentrations in the rat. 14 76

Albuterol (salbutamol), a beta 2 adrenoreceptor agonist, produced a dose-dependent decrease in food intake in Sprague-Dawley male control rats. This phenomenon appeared to be impaired in streptozotocin (STZ) diabetic rats. The density of beta 2 adrenoreceptors in the ventromedial hypothalamic nucleus was increased as a function of diabetes. In contrast, a decrease in the ventromedial hypothalamic 5-hydroxyindoleacetic acid (5-HIAA) concentration, an indicator of serotonin (5-hydroxytryptamine; 5-HT) release or turnover rate, was observed in this disease state. Neither the beta 2 adrenoreceptor level nor 5-HT turnover rate was altered in the periventricular hypothalamic nucleus of STZ diabetic rats. The concentrations of 5-HT in both hypothalamic nuclei were unchanged in these animals. Neurochemical and behavioral abnormalities featured in the diabetic state were reversed with institution of insulin therapy. These data conclude that diabetes-related impairment in the anorexic action of albuterol may be due to derangements in ventromedial hypothalamic beta 2 adrenoreceptor function.
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PMID:Impairment of albuterol-induced suppression of food intake in diabetes mellitus. 137 15

This study examined the microvascular response to serotonin (5-hydroxytryptamine; 5-HT) in short-term streptozotocin-induced diabetic rats. 5-HT was applied topically to the neurovascularly intact and environmentally controlled cremaster muscle of the two-week diabetic rat. Intravital microscopy was used to measure the diameters of large arterioles (First-order; A1) and small arterioles (Third-order; A3), and the FITC-albumin leakage in small venules (Third-order; V3). The diabetic animals were divided into two groups based on the dilator capacity of the A3 arterioles: the Diabetic-Tone group had a dilator capacity of 98 +/- 14.5% compared to 11 +/- 4.1% for the Diabetic No-Tone animals. 5-HT caused significantly greater constriction of A1 arterioles in Diabetic-Tone animals (-40 +/- 6%) than in either the Control (-19 +/- 6%) or Diabetic No-Tone (-18 +/- 5%) animals. 5-HT dilated the A3 arterioles to a similar degree in both the Diabetic-Tone and Control groups, but the Diabetic No-Tone group did not dilate to 5-HT because the A3 arterioles in these animals possessed no basal tone. Control animals showed a large 5-HT concentration-dependent increase in leakage of albumin in V3 venules, but this response was inhibited in the Diabetic-Tone animals. The 5-HT-induced leakiness in the Diabetic No-Tone group was intermediate between the other two groups. These results show that large arteriole constriction and small venule permeability responses to 5-HT are altered early in the development of diabetes, and are different in those animals with and without basal arteriolar tone. These data suggest that streptozotocin-induced diabetes alters microvascular function in striated muscle by at least two different cellular mechanisms.
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PMID:Alteration of microvascular responses to serotonin in the diabetic rat. 150 31

Serotonin (5-hydroxytryptamine, 5HT) is believed to play a role in vasospasm and increased platelet aggregability that in turn could contribute to atherosclerosis. The present study was designed to evaluate a possible participation of serotonin in the development of vascular complications in diabetes mellitus. Whole blood and plasma serotonin, the platelet uptake and release of the amine and serotonin- induced platelet aggregation were studied in 32 patients with Type 2 diabetes. The patients were divided into three groups according to the presence and advancement of retinopathy. Mean levels of blood serotonin content were significantly lower in diabetic patients. The concentration of the amine in the plasma was markedly increased in diabetes. It was correlated with vascular changes of the retina. We established that platelets from diabetic patients took up less serotonin when compared to the control group. Concomitantly enhanced spontaneous release of 5HT from platelets was observed. The platelets of diabetic patients showed increased response to serotonin. There was a relation between serotonin-induced aggregation and the presence of retinopathy. These results suggest that serotonin may be involved in the pathogenesis of diabetic vasculopathy.
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PMID:Blood serotonergic mechanisms in type 2 (non-insulin-dependent) diabetes mellitus. 151 34

This paper attempts to provide a short review of the evidence for: 1. Increased platelet production of thromboxane A2 and reduced vascular production of prostacyclin in the human and also animal models of diabetes. 2. Reduced depressor responsiveness to arachidonic acid of anaesthetized alloxan- and streptozotocin-induced diabetic rats. 3. Enhanced constrictor responsiveness to arachidonic acid in blood-perfused hindquarters of alloxan-induced diabetic rats. 4. Potentiation by the thromboxane A2-mimetic, U46619, of constrictor responses to 5-hydroxytryptamine in Krebs'-perfused hindquarters and kidneys of both control and alloxan-induced diabetic rats. 5. Alterations during diabetes in production of, and responsiveness to, eicosanoids may contribute to the cardiovascular changes which occur in this disease.
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PMID:Cardiovascular sensitivity changes to eicosanoids in rats with experimentally induced diabetes mellitus. 162 40

The aim of this study was to investigate the possibility that inadequate venous return to the heart in diabetes is the result of a neuropathy which affects autonomic nerves supplying the splanchnic vasculature. Mesenteric veins from rats with streptozotocin-induced diabetes were markedly dilated in vivo compared to veins from control animals. Dilation appeared to be the result of loss of muscle tone rather than hypertrophy or hyperplasia of the vessel wall. Using quantification by image analysis and double-labeling immunohistochemistry on mesenteric veins, significant reductions in the density of nerve plexuses staining for 5-hydroxytryptamine (5-HT) and tyrosine hydroxylase (TH) were shown in vessels from diabetic rats compared to controls. No reductions were observed in the density of nerve plexuses stained for the neuronal marker, PGP 9.5, or for substance P (SP), a marker for afferent nerve fibers. These results indicate neurochemical deficits in experimentally induced diabetes which are specific to perivascular noradrenergic nerves and which, within the time-scale of our experiments, do not involve loss of nerve fibers. These deficits may contribute to an increase in venous pooling of blood in the splanchnic vasculature of diabetic rats and thus to inadequate venous return to the heart.
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PMID:Streptozotocin-induced diabetes in rats causes neuronal deficits in tyrosine hydroxylase and 5-hydroxytryptamine specific to mesenteric perivascular sympathetic nerves and without loss of nerve fibers. 167 74

Responses of the basilar artery and aorta to vasoactive agents in alloxan-induced diabetic and age-matched control rabbits were examined. There were no significant differences in the reactivity of the basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT), and K+ between age-matched control and diabetic rabbits. The maximal contraction of the aorta with endothelium in response to NE was significantly enhanced in the case of the aorta from diabetic rabbits. Pretreatment with 10(-6) M methylene blue or removal of the endothelium enhanced the contractile response of aorta to NE from control rabbits and, after such treatment, the concentration-response curve to NE was almost identical to that of aorta from diabetic rabbits. Basal levels of cyclic GMP but not cyclic AMP in the diabetic aorta with endothelium were significantly lower than those in the control aorta with endothelium. These results demonstrate that the cerebral artery is resistant to diabetes mellitus within 10 weeks as compared with the peripheral artery. The enhancement in the contractile response of aorta to NE in diabetic rabbits is due to the attenuation of the spontaneous release of endothelium-derived relaxing factor, through an impairment of the function of endothelial cells.
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PMID:Differences in vascular responses to vasoactive agents of basilar artery and aorta from rabbits with alloxan-induced diabetes. 169 18

These experiments examined the effects of restraint stress on dopamine (DA) and 5-hydroxytryptamine (5-HT) and their principal metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), respectively, in 4 brain regions, as well as on plasma corticosterone concentration (CORT) and behavior in streptozotocin-induced diabetic rats and nondiabetic controls. Diabetic rats had widespread reductions in DA and 5-HT turnover (DOPAC/DA and 5-HIAA/5-HT ratios). Restraint led to equivalent increases in DA turnover in diabetics and nondiabetics, but attenuated increases in 5-HT turnover in diabetic rats. CORT concentration of diabetics and nondiabetics measured in complete quiet did not differ. Relative to these measures, only diabetics had elevated CORT when either restrained or kept in the same room with restrained rats with food and water removed. Open-field exploration was suppressed by restraint in diabetics only. All diabetic rats showed decreased locomotion in a novel environment which was normalized during a second exposure to the apparatus. Together, these results suggest that diabetes-induced disruptions in open-field activity are related to anxiety rather than to motor or energy deficits, and may be related to impaired 5-HT and CORT systems.
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PMID:The functional significance of biochemical alterations in streptozotocin-induced diabetes. 172 17

Streptozocin-induced diabetic (STZ-D) mice have reduced brain concentrations of tryptophan, a precursor substance for 5-hydroxytryptamine, and show lengthened immobility in Porsolt's swim test, a putative animal model of depression. This study investigated whether tryptophan affects behavior in Porsolt's swim test in STZ-administered male National Institutes of Health Swiss mice. In addition, the effect of tryptophan on behavior in the resident-intruder test of aggression was studied. Tryptophan is effective in the treatment of mild depression and may reduce aggressive behavior. Diabetes was induced with injection of 200 mg/kg body wt i.p. STZ. Two weeks after STZ treatment, the mice received 0, 50, and 100 mg/kg i.p. tryptophan 60 min before the swim test. The STZ-administered mice exhibited lengthened immobility in the swim test, and tryptophan caused a dose-related shortening in their immobility times. The control and STZ mice, which were isolated for 1 wk before the resident-intruder test, did not show any difference in the time spent in social investigation or aggressive or defensive behaviors. However, 100 mg/kg i.p. tryptophan 60 min before the test reduced the social interaction and aggressive behavior of the STZ-D mice but increased these behaviors in controls. Results indicate that tryptophan shortens the increased immobility time and reduces social and aggressive behavior in STZ-D mice. Therefore, the reported reductions in the brain-tryptophan concentrations in STZ-D mice may participate in regulating their behavior.
Diabetes 1991 Dec
PMID:Effects of tryptophan on depression and aggression in STZ-D mice. 175

The influences of chronically diabetic states on contraction and relaxation responses of the isolated basilar artery and aorta to various vasoactive agents were examined in alloxan-induced diabetic rabbits with 2 years duration. There were no significant differences in the reactivities of basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT) and KCl between age-matched control and diabetic rabbits. Maximal contractions of aorta with endothelium in response to NE and 5-HT were significantly enhanced in case concentration-response curves for NE and 5-HT-induced contractions in the aorta without endothelium from diabetic rabbits were not different from those from age-matched control rabbits. Acetylcholine-induced relaxations in both the basilar artery and aorta from diabetic rabbits were significantly attenuated compared with those from age-matched control rabbits. However, no differences were observed in concentration-response curves for sodiumnitroprusside-induced relaxations in both the basilar artery and aorta between diabetic rabbits and age-matched control rabbits. These results indicate that chronic diabetes induces an specific enhancement in the contractile responses to NE and 5-HT in aorta and an attenuation in the endothelium-dependent relaxation in both the basilar artery and aorta. These results further demonstrated that the cerebral artery is resistant to diabetes of 2 years duration as compared with the peripheral artery.
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PMID:Effects of chronic diabetes on vascular responses of basilar artery and aorta from rabbits with alloxan-induced diabetes. 180 Nov 4


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