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

There are conflicting data in the literature regarding the role of monamines in the secretion of insulin. In order to clarify the contribution that species variation may make to these divergent results, the uptake of serotinin (5-HT), dopamine (DA), and their precursor amino acids, 5-hydroxytryptophan (5-HTP) and L-dopa, into islets was studied. Islets from golden hamsters, rabbits, guinea pigs, and obese, hyperglycemic mice were isolated by the collagenase technique. The islets were incubated in Krebs-Ringer buffer in the presence of 14C-labeled monamines or their precursors. At 30-minute intervals after initiating the study, the incubation mixture was passed through a Millipore filter. The retained islets were disrupted by sonication and the radioactivity counted. The ratio of the uptake of 5-HTP to 5-HT was at least 3:1 in the hamster, guinea pig, and mouse. In the rabbit the ratio was 1:1. A similar relationship was noted for the uptake of L-dopa and DA. The in-vitro results were confirmed by the in-vivo studies, in which hamsters were injected with 14C5-HT or 5-HTP, followed by isolation of the islets. We conclude that there is significant species variation inthe uptake of these monoamines and their precursors.
Diabetes 1977 Apr
PMID:Species variation in pancreatic islet monoamine uptake and action. 32 Dec 87

Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HT through the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with p-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T3, T4 and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T3 and T4, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HT turnover.
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PMID:Streptozotocin-induced decreases in serotonin turnover are prevented by thyroidectomy. 127 45

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

Amphetamine-induced stereotypy and turnover of dopamine (DA) and serotonin (5-HT) in the CNS were assessed in streptozocin-induced diabetic rats 48 h after withdrawal from insulin treatment and compared with nondiabetic controls, diabetic rats receiving continued insulin treatment, and chronically hyperglycemic diabetic rats. Stereotypy was attenuated in chronically hyperglycemic diabetic rats but normalized in insulin-treated diabetic rats. Stereotypy in insulin-withdrawn rats was intermediate, being attenuated significantly relative to controls but not significantly different from either insulin-treated diabetic rats or chronically hyperglycemic diabetic rats. DA turnover was significantly reduced in striatum and hypothalamus in all diabetic groups. 5-HT turnover was reduced in chronically hyperglycemic diabetic rats in all four brain regions but normalized in insulin-treated diabetic rats. Insulin-withdrawn diabetic rats had significantly reduced 5-HT turnover in frontal cortex. Taken together, the findings indicate that insulin replacement does not normalize diabetes-induced reduction in DA turnover and that short-term insulin withdrawal, e.g., occurring clinically with noncompliance, affects both 5-HT turnover in some brain regions and behavior.
Diabetes 1991 Feb
PMID:Altered behavior and neurochemistry during short-term insulin withdrawal in streptozocin-induced diabetic rats. 167 78

Metabolic and biochemical adaptations were compared in streptozotocin-diabetic and nondiabetic control rats exposed for 24 hours to a cold environment (4 degrees C) or hypobaric hypoxia (simulated altitude = 12,000 ft). In the cold, diabetic rats had greater reductions in adrenal norepinephrine (NE) and greater elevations in urinary NE and epinephrine excretion. However, diabetics did not increase food intake, whereas cold-exposed nondiabetic rats did. 5-HT turnover was reduced in hypothalamus and elevated in brain stem in both diabetics and nondiabetics. Responses to hypoxia were different. Both diabetics and nondiabetics reduced food and water intake and had elevated plasma glucose concentrations. Diabetics had elevated urinary NE excretion. Hypothalamic NE concentration and dopamine turnover were significantly reduced by hypoxia. Brain stem 5-HT turnover was also reduced in nondiabetics but not in diabetics. Thus, diabetics had a different response profile to the environmental stressors than nondiabetics. In addition, the two stressors elicited different responses. Some stressors may be more debilitating in diabetics. The greater reactivity of the sympathetic nervous system in diabetics suggests a mechanism by which stress leads to increased risk of metabolic complications in diabetes mellitus.
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PMID:Altered responses to environmental stress in streptozotocin-diabetic rats. 169 36

Principal objectives in obesity management comprise the prevention of weight gain, the promotion of weight loss, and the treatment of obesity-related complications, including diabetes, hypertension, and depression. Serotonin agonists reduce food intake. The resultant weight loss is variable and there appears to be no way of predicting good responders, nor is there evidence that additional weight loss attributable to drug therapy is sustained once treatment is discontinued, although nonpharmacological strategies for preventing weight regain are worthy of exploration. Serotonin agonists are of clinical value if there is a short-term need for weight reduction or if long-term pharmacotherapy can be justified. This implies that sometimes the dangers of the obese state outweigh the potential hazards of drug treatment. Clearly, if the same agent also improves diabetic control, blood pressure, or depression then a longer term usage is more readily justified. The extent to which this may be achieved by the currently available 5-HT agonists is discussed.
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PMID:Appraisal of the clinical value of serotoninergic drugs. 172 33

Pathological, muscular arteries (common and superficial femoral [FC, FS], anterior and posterior tibial [TA, TP] arteries) of patients suffering from arteriosclerosis obliterans (ASO), thromboangiitis obliterans (TAO), and diabetes mellitus (DIA), removed during amputation of the lower limb were studied as isolated organs. The vessels were cut into transverse rings and contractile force was measured isometrically. The total number of used rings was 828. The following agonists were applied: KCl (80 mM), serotonin (5-HT) (10 microM), prostaglandin F2 alpha (PGF2 alpha) (0.1 mM) or phenylephrine (PE) (10 microM). It was established that applying KCl, 5-HT or PGF2 alpha, the majority of arterial rings display a contraction, but most of the preparations (66%) give no response against PE. The measure of contraction depends on the diagnosis (TAO greater than ASO greater than DIA), on the age of patient and also the anatomical location of the artery in the case of TAO (TP greater than greater than TA), on the associated hypertension in the case of ASO (normotensive greater than hypertensive) and finally on the time elapsed between the operation and usage of preparation if the agonist is KCl. As a conclusion, despite the terminal clinical stage the majority of studied human arteries retained at least a part of their functional integrity.
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PMID:[Experiences with isolated organ studies on pathological human arteries]. 187 91

Concentrations of monoamines and their metabolites were investigated in various brain regions of 3, 50, and 100 days diabetic mice. An increase in the content of norepinephrine was observed in the pons-medulla and striatum in short-term (3 days) diabetic mice, and could be sustained for 100 days and 50 days, respectively. In the hypothalamus and cortex, the increase of norepinephrine was observed in both 50 and 100 day diabetic mice, but that of cerebellum was only observed in the 100 day diabetic mice. The concentration of dopamine was increased in the striatum both in short-term and long-term (50 and 100 days) diabetic mice, that of pons-medulla and cortex was increased in the long-term diabetic mice. Concentrations of the acidic metabolites of dopamine, dihydroxyphenylacetic acid and homovanillic acid were decreased in the hypothalamus, hippocampus and striatum, while increased in the pons-medulla and cortex. 5-Hydroxytryptamine concentration was increased in the hypothalamus, hippocampus, pons-medulla and cortex progressively from short-term to long-term diabetic mice. However, the concentration of its acidic metabolite, 5-hydroxyindoleacetic acid, was decreased in the hypothalamus, hippocampus, striatum, pons-medulla and cortex. These data suggest that diabetes is associated with a significant disturbance of brain monoamine metabolism. This disturbance was not generalized but related to some specific areas of the brain and some of these alterations were progressive from short term to long term diabetes.
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PMID:Effects of short and long-lasting diabetes mellitus on mouse brain monoamines. 191 76


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