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

Urinary bladder function was examined in the spontaneously diabetic BB rat six months after the onset of diabetes. Diabetes caused significant decreases in rat weight and increases in bladder body weights and in vivo bladder capacities compared to age-matched controls, but no changes in the weights of bladder bases. The absolute contractile responses of urinary bladder body and base strips to nerve stimulation, carbachol, 5-hydroxytryptamine, ATP, phenylephrine, and KCl were unaltered by diabetes. However, when the data were corrected for tissue mass, there were slight but not significant decreases in contractile responses of strips from diabetic rats. There were increases in total muscarinic receptor numbers and calcium channel binding sites in bladder bodies from BB rats as a result of the increases in tissue mass. The data indicate that the six month-diabetic BB rat differs from the streptozotocin-diabetic rat in the sensitivity of the urinary bladder to the complications of diabetes, probably as a result of the insulin treatment required to keep BB rats alive.
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PMID:Urinary bladder function 6 months after the onset of diabetes in the spontaneously diabetic BB rat. 184 33

1. Genetic databases are an expanding and readily accessible repository of information on the mapping and sequencing of the human genome, and that of other model organisms. The integration and application of this information to neuropsychiatric disease is illustrated using neuroendocrine and neuropharmacologic data, computerized and other genetic databases. 2. This computer-assisted integrated approach to knowledge structures permits the rapid generation of hypotheses, the prompt identification of candidate gene loci, an explanation for genetic heterogeneity, and strategies for the use of potential linked markers. 3. Results using this integrated search strategy demonstrate that over 30 candidate loci for neuropsychiatric disease have currently been mapped in man (spread over 14 chromosomes in the human genome), and that at least 6 homologous loci have been mapped in mouse. 4. Using a metabolic pathway approach, it can be shown that the best current candidate gene locus for a subtype of schizophrenia located on chromosome 5q11-13 (HGML10 # SCZD1 and OMIM #181510) is in the serotonergic pathway, i.e. a receptor for 5-hydroxytryptamine (subtype 1A; HGML10 #HTR1A) which also maps in the same chromosomal region. 5. Parallels are suggested between inborn errors of metabolic pathways in the somatic endocrine system (using insulin-dependent diabetes mellitus as a paradigm) and the neurotransmitter and hormonal systems within the brain. 6. A subset of neuropsychiatric disorders may thus be viewed as inborn errors of cerebral metabolic pathways primarily affecting the biogenic amine pathways.
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PMID:Integrated genetic databases in the study of neuropsychiatric diseases: inborn errors of cerebral metabolic pathways? 187 20

A survey shall be given on the physiological, pathophysiological and pharmacotherapeutic backgrounds of the biogenic amine 5-hydroxytryptamine (serotonin; 5HT), to be preceded by a few historical remarks. 5HT is biosynthesized from L-tryptophan via hydroxylation and subsequent decarboxylation. 5HT is predominantly found in enterochromaffin cells, platelets and in various structures of the central nervous system. Its concentration in circulating blood is low and probably subthreshold. Whereas the physiological role of 5HT is rather unclear, 5HT appears to play a relevant role in certain psychiatric disorders, in migraine and the carcinoid syndrome. Its role in essential hypertension remains uncertain. However, 5HT appears to contribute to and to exacerbate the damage to blood vessels which were already predamaged by atherosclerosis, diabetes mellitus or possibly old age as such. A major breakthrough in the pharmacology of the serotonergic system was achieved by the discovery of several subtypes of 5HT receptors, with a corresponding collection of selective agonists and antagonists towards these receptor subtypes. This development is the basis of various drugs which interact with the serotonergic system and its receptors, like the various 5HT2 receptor antagonists (of which ketanserin is the prototype), methysergide, pizotifen, urapidil, flesinoxan and a variety of psychoactive drugs. The most important of these drugs and their potential application will be discussed with an emphasis on cardiovascular disorders.
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PMID:Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs. 213 70

The effect of progression of diabetes on adrenergic, serotonergic, and peptidergic innervation of the proximal colon of the rat at 8, 16, and 25 wk after induction of diabetes with streptozotocin was investigated using immunohistochemical, biochemical, and immunochemical methods. Two different responses to diabetes emerged from the present study. The first response, which involves noradrenaline and vasoactive intestinal peptide, was characterized by a sign of degeneration, where there was an initial increase in tissue level and immunoreactivity of the transmitters followed by a decrease in tissue level and density of nerve fibers at 16 and 25 wk after induction of diabetes. The second response, which involves 5-hydroxytryptamine, substance P, and calcitonin gene-related peptide, was characterized by changes in tissue level and immunoreactivity of the transmitters with no evidence of degeneration. The third feature was one of resistance to change due to diabetes, which was demonstrated by neuropeptide Y-containing nerves, where there was neither a change in tissue level of neuropeptide Y nor a change in immunoreactivity. It seems likely that the overall changes described will have profound implications in the function of the gut in the streptozotocin-diabetic rat model that may have some parallels in diabetic humans.
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PMID:Progressive changes in adrenergic, serotonergic, and peptidergic nerves in proximal colon of streptozotocin-diabetic rats. 245 87

The influence of thyroxine treatment on the altered reactivity of the isolated perfused mesenteric vasculature from streptozocin-induced diabetic rats was examined and compared with that of insulin. After 8 weeks of diabetes, the time when the decreased response to isoproterenol appeared, treatment with thyroxine reversed this decreased response to control levels. However, thyroxine replacement did not reverse the decreased responsiveness to norepinephrine, 5-hydroxytryptamine, acetylcholine, and isoproterenol after 12 weeks of diabetes. On the other hand, insulin replacement improved the vascular responsiveness to these agonists at 8 and 12 weeks. Insulin treatment also reversed the attenuated response to nerve stimulation found in diabetic rats, whereas thyroxine treatment did not improve it. Insulin treatment reversed the decreased plasma thyroid hormone levels similarly as thyroxine treatment. These results suggest that thyroid hormone deficiency is likely to be involved partly in the altered reactivity of the rat mesenteric vasculature at the early period of diabetes. On the other hand, adrenergic neuropathy is not induced by hypothyroidism.
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PMID:Reversal effect of thyroxine on altered vascular reactivity in diabetic rats. 247 Sep 87

Neurochemical and metabolic effects of acute (immobilization for 2 h) and chronic (immobilization for 2 h/day for 4 consecutive days) stress were investigated in diabetic female rats either pretreated 1 week or 5 weeks earlier with streptozotocin (STZ). Hypothalamic serotonin (5-hydroxytryptamine, 5-HT) metabolism was estimated by measuring the respective levels of 5-HT precursor, the amino acid tryptophan (TRP), 5-HT and the 5-HT metabolite, namely 5-hydroxyindoleacetic acid (5-HIAA). To assess the respective metabolic effects of stress and diabetes, plasma total TRP, insulin, glucose and corticosterone levels were measured. Short- and long-term STZ treatment triggered marked decreases in plasma total TRP and hypothalamus TRP levels but the diabetogenic agent diminished 5-HT metabolism in the 1-week ST-treated rats only. Acute stress promoted a marked decrease in plasma total TRP in the vehicle-treated rats and in the 1-week-diabetic rats, which was associated with significant increases in hypothalamic TRP and 5-HIAA levels. In the 5-week-diabetic rats, a single restraint affected neither peripheral and central TRP levels nor hypothalamus 5-HT metabolism. Acute stress triggered hypercorticosteronemia in all groups of rats but it promoted hyperglycemia and hypoinsulinemia in the vehicle-injected rats only. Twenty-four hours after the fourth immobilization, plasma total TRP was reduced in the vehicle-injected rats only with no effect on hypothalamic levels of TRP. On the other hand, chronic restraint was found to reduce exclusively hypothalamus 5-HT and 5-HIAA levels in the 5-week-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Duration of streptozotocin diabetes influences the response of hypothalamic serotonin metabolism to immobilization stress. 247 66

1. Vascular responsiveness was examined in aortic ring preparations, with or without endothelium, from rats with experimental diabetes induced by streptozotocin and from vehicle-treated (control) rats. 2. There were no significant differences between diabetic tissues and control tissues in the responsiveness to the vasoconstrictors noradrenaline, 5-hydroxytryptamine and KCl, and to the vasodilators sodium nitroprusside, isoprenaline and acetylcholine. 3. When maximum contractions to vasoconstrictors was expressed relative to tissue weight, maximum contractions were significantly greater in diabetic tissues. 4. When expressed in terms of the KCl contraction, there were no significant differences between diabetic and control tissues in the maximum contraction to vasoconstrictors. 5. These results demonstrate that diabetic-induced changes in vascular responsiveness, if any, do not occur at the receptor level.
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PMID:Effects of experimental diabetes on the responsiveness of rat aorta. 279 Mar 73

The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta E) and immunoreactive insulin (IRI) was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) 3 days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for 3 days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) while it caused significant increase and decrease in brain beta E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta E and insulin regardless of the availability of pancreatic insulin.
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PMID:Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat. 293 73

Previous work by other authors has shown that alloxan-induced diabetes increases whereas streptozotocin-induced diabetes does not alter nonesterified fatty acid (NEFA) plasma levels. The present study replicates these results and demonstrates that fasted, streptozotocin-induced diabetic animals also have increased NEFA levels. In addition, brain levels of 5-hydroxytryptamine (5-HT) and of its immediate precursor and metabolite were measured. Alloxan- and fasted, streptozotocin-induced diabetic rats showed significant increases in brain indoleamine concentrations, whereas fed, streptozotocin-induced diabetic rats had unchanged levels of the same compounds. Levels of brain indoleamines exhibited a strong positive correlation with wet-dog shakes (an index of 5-HT activity) elicited by hippocampal stimulation. Blockade of wet-dog shakes by 5-HT receptor antagonists strengthens the proposal that this behavior is a good index of central 5-HT activity. The increased content of brain indoleamines in alloxan- and fasted, streptozotocin-induced diabetic rats may be related to the increased NEFA plasma levels seen in the same animals. This hypothesis is supported by the positive correlation demonstrated between NEFA and 5-HT levels. In conclusion, it is suggested that alloxan-induced diabetes may represent a useful model for studying the various behavioral changes known to occur in diabetics.
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PMID:Brain indoleamines in alloxan- and streptozotocin-induced diabetic rats. 297 May 24

Platelet-rich plasma was prepared from 47 patients with non-insulin-dependent diabetes treated with glibenclamide and metformin, and 21 controls. The release of radio-labelled 5-hydroxytryptamine in response to aggregating agents (adenosine diphosphate, adrenaline and sodium arachidonate), and the effects on release of a selective thromboxane inhibitor (UK-34787) were investigated. Subsequently, 20 of the diabetic subjects were chosen at random for treatment with insulin; the remainder continued to take tablets. Platelet studies were then repeated, in all patients, after 4 and 6 months. The results showed an association between platelet behaviour and the presence of vascular complications, and were consistent with previous observations of reduced platelet reactivity in patients taking sulphonylureas. There was no correlation of platelet reactivity with blood glucose, glycosylated haemoglobin or lipid levels.
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PMID:Platelet behaviour in non-insulin-dependent diabetes--influence of vascular complications, treatment and metabolic control. 309 92


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