Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of streptozotocin (STZ)-induced diabetes and a combination of chronic treatment with haloperidol (HPD) on dopamine (DA)D2, serotonin (5-HT) 5-HT1A and 5-HT2A receptors was investigated in rat brain. Rats were randomly assigned to one of four groups: vehicle-vehicle, STZ-vehicle, vehicle-HPD, and STZ-HPD groups. Four weeks after single administration of STZ (65 mg/kg IV) or vehicle (citrate buffer), rats received depot HPD (4 mg/kg IM) or vehicle (sesame oil) once a week for 4 weeks. Sixteen days after the last injection of HPD or vehicle, rats were sacrificed, and the density of binding sites was determined using [3H]spiperone as ligand in the striatum (D2),[3H]8-hydroxy-2-(di-n-propyl)-aminotetraline in the hippocampus (5-HT1A), and [3H]ketanserin in the frontal cortex (5-HT2A). The density of D2 receptors was significantly increased in the vehicle-HPD compared to vehicle-vehicle controls. However, striatal D2 receptor density of the STZ-HPD and the STZ-vehicle were not significantly different from the vehicle-vehicle group. A significant increase in cortical 5-HT2A receptor density was observed only in the group of STZ-vehicle. Treatment with STZ, HPD, or the combination thereof, did not affect the density of 5-HT1A receptors. The affinity constants for D2, 5-HT1A, and 5-HT2A receptors were not affected by any treatment. These results suggest that diabetic state may affect brain serotonergic activity via an increase in the density of 5-HT2A receptors. This may indicate an increased vulnerability to major depression in patients with diabetes. The lack of an effect of the combined chronic treatment with STZ and HPD on the D2 receptor density may correspond to the increased risk to develop tardive dyskinesia in patients with diabetes.
 ...
PMID:The effect of streptozotocin-induced diabetes on dopamine2, serotonin1A and serotonin2A receptors in the rat brain. 913 34

Diabetic animals exhibit altered neurotransmission in brain monoaminergic systems. By means of in situ hybridization, we have investigated the expression of dopamine, noradrenaline, and serotonin transporter (DA-T, NA-T, and 5-HT-T, respectively) mRNAs in the brains of alloxan- and streptozotocin-diabetic rats. The expression of DA-T mRNA is decreased in 1- (-11%) and 4- (-17%) week alloxan-diabetic and 4- (-9%) and 8- (-20%) week streptozotocin-diabetic rats in the ventral medial bundle. The expression of NA-T mRNA is decreased in the locus coeruleus of 8- (-26%) week streptozotocin-diabetic rats, in the noradrenergic A1 cell group of 4- (-27%) week alloxan- and 8- (-25%) week streptozotocin-diabetic rats, and in the noradrenergic A2 cell group of 1- (-21%) and 4- (-28%) week alloxan-diabetic and 4- (-27%) and 8- (-25%) week streptozotocin-diabetic animals. The expression of 5-HT-T mRNA in the dorsal raphe nucleus is increased in 1- (+14%) and 4- (+44%) week alloxan- and 4- (+28%) and 8- (+44%) week streptozotocin-diabetic rats. The expression of each of the three monoamine transporter genes may be differentially regulated in diabetes and dependent on the duration of diabetes. Altered monoamine transporter gene expression may possibly contribute to the observed dysfunctions in brain monoamine transmission in chronic diabetes.
 ...
PMID:Monoamine transporter gene expression in the central nervous system in diabetes mellitus. 916 37

In order to clarify the effect of exogenous corticotropin-releasing factor (CRF) on catecholaminergic and serotoninergic system activity in the mediobasal hypothalamus-median eminence (MBH-ME) of ewes the changes in extracellular levels of noradrenaline (NA) and serotonin (5HT), and main metabolites of monoamines, 4-hydroxy-3-methoxyphenylglycol (MHPG), 3,4-dihydroxy-phenylacetic acid (DOPAC), homovanilic acid (HVA), and 5-hydroxy-indolo-3-acetic acid (5-HIAA) were quantified in the perfusates collected from MBH-ME. NA, 5-HT and monoamine metabolites in the perfusates were analyzed using high performance liquid chromatography with electrochemical detection. CRF induced a rise in extracellular concentration of NA and 5-HT only in the estrous ewes prior to a preovulatory LH surge. CRF treatment caused a heterogenous effect on extra-cellular concentrations of 5-HT in ewes during the preovulatory LH surge. Except for DOPAC and HVA in some estrous ewes during the preovulatory LH surge, CRF caused an increase in monoamine metabolites levels in the MBH-ME in anestrous and estrous animals. These results indicate that CRF facilities NA release in the MBH-ME during the presurge LH period in ewes, and that CRF increases metabolic activities of the monoaminergic systems in this structure in the anestrous and estrous ewes, except dopaminergic system in the ewes during the preovulatory LH surge. It is suggested that: 1) the responses of monoaminergic systems activity in the MBH-ME to CRF in large degree is dependent upon physiological state of ewes and 2) in some endocrinological phases CRF may affect LHRH and other hypothalamic hormone secretion indirectly by altering monoaminergic system activity in the MBH-ME.
Exp Clin Endocrinol Diabetes 1997
PMID:Extracellular monoamines and their metabolites in the mediobasal hypothalamus--median eminence of anestrous and estrous ewes during CRF treatment. 922 15

As many as 25 percent of patients with diabetes mellitus may also have depressive symptoms. Tricyclic antidepressants (TCAs) may produce increased appetite and weight gain with adverse consequences for diabetes. The selective serotonin reuptake inhibitors (SSRIs), however, may improve fasting blood sugar in laboratory studies. In an initial application, sertraline was administered at a dose of 50 mg/day in a 10-week open study to 28 non-insulin-dependent diabetes mellitus (NIDDM) patients with DSM-III-R major depression after a 2-week single-blind placebo washout period with a minimum 17-Item Hamilton Rating Scale for Depression (HAM-D) score of 18. The patient group included 16 males and 12 females with a mean age of 54.2 +/- 8.8 years. Results indicated (1) significant improvement in mean HAM-D (22.6 +/- 3.4 to 4.9 +/- 5.9, p < .001) and in mean Beck Depression Inventory (BDI) scores (21.9 +/- 10.5 to 12.7 +/- 8.3, p < .001); (2) fall in platelet serotonin (5-HT) content (79.7 +/- 22.5 to 13.6 +/- 12.7 ng/10(8) platelets, p < .001); (3) correlation of baseline platelet 5-HT content with response to sertraline by BDI scores (r = 0.51, p < .05); (4) improved dietary compliance for those with baseline value below 70 percent (59.7% to 69.1%, p < .005); and (5) 13 of 17 patients with baseline glycosylated hemoglobin A (HbA1c) levels greater than 8.0, showed a reduction (p = .018). Sertraline may be an effective antidepressant in patients with diabetes mellitus and response may be predictable by higher baseline platelet 5-HT content, with the potential to improve dietary compliance and reduce HbA1c measures. As with all open studies, replication is essential.
 ...
PMID:Sertraline in coexisting major depression and diabetes mellitus. 923 Jun 40

Chronic uremia is associated with a bleeding tendency, and paradoxically with propensity for thrombotic complications. Several physiological systems are subject to circadian rhythm, including among others hemostasis, platelet aggregability and fibrinolysis. Alterations in these rhythms were suggested to be involved in the pathogenesis of sudden cardiac and cardiovascular complications of diabetes mellitus. As cardiovascular events are the most frequent cause of death in dialyzed patients, we studied circadian rhythm of platelet function in chronically hemodialyzed patients in relation to blood and plasma serotonin. We investigated 16 patients (mean age 49.7 +/- 12.2 years, 10 females, 6 males) who had been maintained on chronic hemodialysis. Control group consisted of 8 age matched healthy volunteers. Blood was collected after 15 min. rest at 8:00, 11:00, 17:30, and 23:00 from antecubital veins. Platelet aggregation was measured according to the method of Born. Following concentrations of aggregating agents were used: ADP 5 microM; collagen, 2 micrograms/ml; arachidonic acid 0.75 microM, serotonin 1 microM; and ristocetin 1.5 micrograms/ml. Serotonin was measured in whole blood and plasma by HPLC method. In PRP from healthy subjects aggregatory responses to ADP and arachidonic acid were significantly higher at 17:30 than at 8:00. In uremic patients aggregatory response to ADP and ristocetin was more intensive at 11:30 and 23:00 in comparison to 8:00. Whole blood 5-HT did not change during the day, while plasma 5-HT concentration increased significantly in uremics at 11:30 in comparison to initial value. In conclusion, our study demonstrates that in chronically dialyzed patients circadian changes in platelet aggregation are different from normal persons.
 ...
PMID:[Altered circadian rhythm of platelet aggregation in patients on longterm hemodialysis]. 929 92

Neurochemical changes in the ventromedial hypothalamus (VMH) after a single intravenous injection of streptozotocin were examined, using in vivo brain microdialysis under free-moving conditions. Although streptozotocin-induced diabetes produced significant decreases in extracellular concentrations of noradrenaline (NA), serotonin (5-HT), and their metabolites in the VMH, the ratios of 3-methoxy-4-hydroxyphenylglycol/NA and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT were increased. Experimental diabetes led to a pronounced increase in extracellular GABA, which correlated strongly with the decrease in dialysate levels of NA, and to a smaller extent with that of 5-HT. A modification of dopamine (DA) metabolism was induced in the VMH of diabetic rats, whereas there was no change in dialysate DA levels. Daily injections of insulin were able to restore their levels to normal in the areas tested in the microdialysis study. The equal increases in dialysate 5-HT and 5-HIAA and the better restoration of the 5-HIAA/5-HT ratio after insulin therapy indicate that serotonergic activity may depend on the levels of circulating insulin more than on noradrenergic activity. Circulating NA was reduced in streptozotocin-diabetic rats, suggesting that the diabetes-induced reduction in sympathetic activity is accompanied by decreases in NA, or 5-HT, or both, in the VMH.
 ...
PMID:Microdialysis study of modification of hypothalamic neurotransmitters in streptozotocin-diabetic rats. 932 91

Streptozotocin (STZ)-elicited diabetes reduces central serotonin (5-hydroxytryptamine, 5-HT) synthesis/metabolism, but whether this reduction leads to decreased release of 5-HT has only scarcely been investigated. We have thus analysed the impact of STZ diabetes on hippocampal extracellular 5-HT levels both under basal conditions and during restraint stress, a procedure known to stimulate hippocampal 5-HT synthesis/metabolism and release. The pretreatment with STZ (3 weeks beforehand) and the 1 h restraint session respectively decreased and increased hippocampal 5-HT metabolism, as assessed by tissue analysis of 5-HT and 5-hydroxyindoleacetic acid. On the other hand, hippocampal microdialysis revealed no difference in basal levels of extracellular 5-HT levels in (conscious) vehicle- and STZ-pretreated rats, but a differential effect of restraint. Thus, extracellular 5-HT levels increased throughout restraint (maximal increase: 194%) in vehicle-, but not in STZ-pretreated rats. In the latter rat group, plasma corticosterone levels were, however, increased, thus indicating a significant aversiveness to stress. Lastly, because anxiety-related behaviours may be affected by hippocampal serotonergic systems, resting and restrained vehicle- and STZ-pretreated rats were compared (immediately after stress) in an elevated plus-maze of anxiety. Pretreatment with STZ reduced the percent number of open arm entries and the number of closed arm entries, indicating increased anxiety and reduced locomotor activity, respectively. Restraint tended to increase anxiety-related behaviours in all rats, but this trend never reached significance. Our results confirm that gross analyses of 5-HT metabolism do not yield information on 5-HT release, and suggest that the prevalence of diabetes among patients suffering affective disorders could be related to the lack of hippocampal serotonergic response to aversive stimuli.
 ...
PMID:Differential effects of restraint stress on hippocampal 5-HT metabolism and extracellular levels of 5-HT in streptozotocin-diabetic rats. 940 74

Depression is a common, life-disrupting, potentially lethal illness that can affect both sexes and all ages. Its peak onset is in the early adult years. It is more common than hypertension in primary care practice. Recent studies show that fewer than 1 in 20 depressed patients are correctly diagnosed and adequately treated. Depression periodically destroys the productivity of those with the condition, and depressed patients have a worse quality of life than patients with debilitating, chronic conditions such as arthritis, hypertension, diabetes mellitus and back pain. Suicide occurs in as many as 15% of patients with depression, especially those with recurrent episodes and hospitalisations, and may even occur in those with in subsyndromal depression. Suicide is one of the leading causes of death, and individuals who complete suicide have usually experienced mood disorders, mainly depression. Current data support a decreased frequency of suicidal ideation with all antidepressants, including selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). Modern pharmacotherapy is the cornerstone for effective treatment of depression. As they are well tolerated, even in the presence of comorbid medical illness, and easier to manage, SSRIs enhance compliance. A fully adequate antidepressant dosage is suitable for patients of all ages and can be used by non-psychiatrist physicians for the treatment of the acute episode, as well as the frequent recurrences that often require long term maintenance antidepressant medication. SSRIs have fewer drug interactions than older antidepressants, and even the SSRI inhibition of hepatic cytochrome P450 enzymes has proven only very infrequently to be of clinical importance. SSRIs also effectively treat anxious depression, dysthymia and atypical depression. Fluoxetine may provide more rapid onset of therapeutic effect because it can be started at closer to its usual full therapeutic dosage than other SSRIs or older antidepressants. SSRIs, in particular fluoxetine, are more suitable for use as long-term maintenance therapy in these chronic relapsing diseases. These factors and the high efficacy rate, increased safety in overdose, reduced incidence of adverse effects (mostly decreasing with time) and superiority in ease of maintaining patients in adequate treatment plans provides fluoxetine with an overall superior therapeutic profile.
 ...
PMID:Risks and benefits of selective serotonin reuptake inhibitors in the treatment of depression. 946 88

Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).
 ...
PMID:Medical treatment of migraine: from mechanisms of action to contraindications. 955 32

Changes in reactivity of vascular smooth muscles of male alloxan-induced diabetes-susceptible (ALS) and resistant (ALR) mice aorta were investigated at 2 weeks, 1, 2 and 4 month(s) after the injection of alloxan (45 mg/kg, i.v.). The glucose levels in blood and urine of all the alloxan-treated ALS mice were markedly elevated while those in alloxan-treated ALR and non-treated ALS and ALR mice were not altered. The magnitude of high K+ (65.4 mM)-induced contractions were not affected by the treatment of alloxan. Norepinephrine-induced contractions in vascular smooth muscles of ALS mice in a diabetic state for 2 or 4 months were significantly potentiated. The contractile sensitivity to prostaglandin F2 alpha (PGF2 alpha) was increased in the 4-month-diabetic state. Responsiveness to 5-HT did not vary in the diabetic mouse. Vasorelaxation induced by nitroprusside was attenuated in 2 weeks, 2 or 4 month-diabetic ALS mice. Similarly the inhibitory effects of levcromakalim were attenuated at 2 and 4 months. The influences of diabetes on the inhibitory effects of forskolin or verapamil were very small or not detected. The effects of the vasomodulators used in this study on the vascular smooth muscles of alloxan-treated ALR mice did not differ from those of untreated ALR mice. The results from using ALS and ALR mice suggest that the vasoreactivities to some vasomodulators are changed especially in the long-term diabetic state and that when diabetes was not induced the dose of alloxan does not have any effect on vascular smooth muscle.
 ...
PMID:Vascular responsiveness in alloxan-induced diabetes-susceptible (ALS) and resistant (ALR) mice. 981 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>