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

Partial alpha 2-agonists are thought to lower blood pressure principally by stimulation of postsynaptic central nervous system alpha 2-adrenoceptors. It is possible for some to have also a peripheral action, either by acting on the inhibitory presynaptic or as an antagonist at the postsynaptic alpha 2-adrenoceptor. In order to assess these other actions, indices are required for these receptors. Plasma growth hormone is used for the central nervous system and skin blood flow for peripheral postsynaptic alpha 2-adrenoceptors. Plasma insulin is also an index for the latter, but a double-site assay is required to detect decreases within the fasting range. Plasma noradrenaline reflects both central nervous system and peripheral modulation of sympathetic nerve activity, so that "dynamic" tests (described next) are required to dissect these two control mechanisms. Selective peripheral alpha 2-adrenoceptor stimulation or blockade may be attractive for various therapeutic applications such as hypertension, diabetes, and Raynaud's phenomenon. The balance of opposing pre- and postsynaptic alpha 2-adrenoceptor effects will be important and this may require more dynamic tests than already mentioned, such as comparing the effect of alpha-methylnoradrenaline on plasma noradrenaline (presynaptic effect) and skin blood flow (postsynaptic effect) in the presence and absence of the partial alpha 2-agonist or antagonist under investigation. Since alpha-methylnoradrenaline does not penetrate the central nervous system, any blockade of its action by a drug must be peripherally mediated. Examples of all these indices, investigations, and drugs are presented.
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PMID:Investigation of alpha 2-adrenoceptors in humans. 257 Dec 94

Diabetes mellitus is known to produce alterations in vascular reactivity. In the present study we have examined the effects of endothelium-dependent and endothelium-independent relaxing substances on thoracic aorta from insulin-dependent (Type-1) and noninsulin-dependent (Type-2) diabetic rats and their appropriate controls. Endothelium-dependent relaxations produced by acetylcholine and histamine in aortic rings precontracted with noradrenaline were significantly increased in insulin-dependent diabetic vessels. In contrast, the relaxations elicited by those agents were significantly attenuated in noninsulin-dependent diabetic aorta preparations. On the other hand, the relaxations induced by sodium nitroprusside (an endothelium-independent relaxant agent) in both types of diabetic preparations were comparable to those in control vessels. The results indicate that insulin-dependent and noninsulin-dependent diabetes lead to specific alterations of the endothelium-dependent relaxation of rat aorta.
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PMID:The effects of type-1 and type-2 diabetes on endothelium-dependent relaxation in rat aorta. 258 91

Peripheral neuropathy is a correlate of experimental diabetes induced in rats by means of a single injection of alloxan. The autonomic and enteric innervation of the gut are profoundly affected in the small intestine of such animals. A complex process of denervation and hyperinnervation of the gut wall of diabetic animals is observed. It was previously reported that the cholinergic parasympathetic innervation of the intestine is markedly reduced. We have found that noradrenergic sympathetic axons hyperinnervate the duodenum of diabetic rats, whereas noradrenaline levels are significantly reduced in the jejunum. The putative enteric neurotransmitter dopamine is also present in higher levels in the duodenum. The intrinsic peptidergic neurons of the gut are deeply affected as well in diabetic rats. Substance P and met-enkephalin content are remarkably reduced throughout the small intestine, whereas vasoactive intestinal polypeptide levels (VIP) are significantly increased in the duodenum. Indeed, immunocytochemical staining of the ileum did reveal hypertrophy of VIP-positive axons in diabetic rats. The intrinsic serotoninergic innervation of the gut is apparently unaffected. Our results indicate that the changes of gut innervation observed in experimental diabetes are consistent with increased content and also likely with hyperinnervation by the neuronal systems involved in smooth muscle relaxation and decreased content and with denervation by those systems with smooth muscle contraction properties. Such a perturbed gut innervation may be responsible of the gastrointestinal dysfunctions that are among the most common complications of diabetes.
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PMID:Denervation and hyperinnervation in the nervous system of diabetic animals. I. The autonomic neuronal dystrophy of the gut. 259 79

We have studied echocardiographic morpho-functional alterations in 34 male subjects with diabetes, aged 31-73 years, with and without autonomic nervous system failure. The subjects are grouped following the tests "deep breathing", "Valsalva manoeuver", "lying to standing" and "active standing" in: D-I (10 normal subjects); D-II (16 subjects with parasympathetic failure); D-III (8 subjects with orthosympathetic failure). The D-III subjects showed significantly lower parietal systolic stress (PSS) compared to normal subjects, 115.6 +/- 17.4 vs 163.1 +/- 13.1 10(3) dynes/cm2 (mean +/- 1SD), and significantly lower end isovolumetric systolic stress, 67.8 +/- 7.8 vs 98.6 +/- 7.1 10(3) dynes/cm2 ("afterload" indexes). In D-III group, the subjects with noradrenaline levels greater than 300 pg/ml, with an hypothetical peripheral resistance to noradrenaline (or receptor "down regulation"), showed higher blood pressure levels and higher parietal stress (PSS: 141.3 +/- 25.3 vs 98.5 +/- 20.7 10(3) dynes/cm2; EISS: 74.1 +/- 17.8 vs 63.6 +/- 8.6 10(3) dynes/cm2). Thus, cardiovascular signs of autonomic failure, like the stress index variation, related to a modification of the afterload, may be observable in diabetic patients.
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PMID:[Afterload changes in diabetic dysautonomia evaluated using echocardiography]. 260 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

Hyperactivity of the sympathetic nervous system has repeatedly been assumed to play a role in the pathogenesis of essential hypertension. Particularly in young hypertensive patients, sympathetic nervous activity seems to be slightly elevated. On the other hand an increased pressor effect of noradrenaline has also been reported in some patients with essential hypertension. While neither the slightly elevated sympathetic tone nor the inconstant increased reactivity to noradrenaline could alone be responsible for the blood pressure elevation, both factors together appear to form an important determinant of the level of arterial blood pressure. There is no uniform evidence that sympathetic nervous activity is changed in uncomplicated diabetes. A diminished sympathetic nervous activity in patients with secondary complications is so far not proved. A slight increase in circulatory reactivity to noradrenaline is described independent of the height of blood pressure, however, data in moderate and accelerated hypertensive diabetic patients are not available.
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PMID:The contribution of the sympathetic nervous system to hypertension in diabetes mellitus. 269 50

Streptozotocin-induced diabetes caused an increase in AP and reactivity to noradrenaline in perfused caudal artery of normotensive rats (WKY). In spontaneously hypertensive rats (SHR) diabetes led to an increase in reactivity not only to noradrenaline but also to alpha 1-agonist phenylephrine; a response to endothelium-dependent agent acetylcholine was decreased. Alterations in function of the vascular endothelium may be one of the factors causing elevation of vasoconstriction in diabetes mellitus.
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PMID:[The vascular response of spontaneously hypertensive and normotensive rats with diabetes mellitus]. 271 81

1. Endogenous noradrenaline release from washed platelets incubated under resting conditions and in the presence of thrombin was examined in 14 normal subjects and 10 subjects with type 1 (insulin-dependent) diabetes. 2. Irreversible aggregation of platelets from both normal and diabetic subjects was induced by thrombin (0.3 unit/ml). Platelets from diabetic subjects were more sensitive than platelets from normal subjects, extents of aggregation being 89% and 76%, respectively (P less than 0.002). 3. Stimulation with thrombin (0.3 unit/ml) elicited marked platelet release of noradrenaline to the incubation medium in both normal and diabetic subjects. Supernatant noradrenaline concentrations obtained under thrombin-stimulated conditions did not significantly differ between normal and diabetic subjects. However, under resting conditions noradrenaline levels were significantly greater (+93%, P less than 0.02) for diabetic than normal subjects. 4. Measurement of platelet noradrenaline contents after thrombin stimulation revealed no difference between normal and diabetic subjects. Under resting conditions, however, platelet noradrenaline levels were significantly lower (-46%, P less than 0.02) for diabetic than normal subjects. Thus, in the diabetic subjects increased resting platelet efflux of noradrenaline is mirrored by a decreased platelet noradrenaline content. 5. A consequence of increases in resting catecholamine efflux may be enhanced platelet activity resulting in increased platelet aggregation.
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PMID:Platelet efflux of noradrenaline in patients with type 1 diabetes mellitus. 273 79

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

The question of diabetic neuropathy was studied in the field-stimulated isolated vas deferens of the mouse. The animals were treated with either buffer or streptozotocin (170 mg/kg i.v.) 2 or 4 weeks, respectively, beforehand. Stimulus-response relationships were tested by variation of frequency (VF) at constant pulse width and by variation of pulse width (VP) at constant frequency. The adrenergic twitch component was eliminated by prazosin (1 microM) and the purinergic component by alpha, beta-methylene ATP (MeATP, 10 microM). The diabetes did not alter the muscular contractility (tested with KCl) and left the twitch-inhibiting effects of prazosin and MeATP unchanged, thereby revealing no difference in susceptibility between noradrenergic and purinergic mechanisms. However, in diabetic vasa, the maximal effectiveness of stimulation was decreased with VF but not VP, whereas the sensitivity of intramural neurons (50% effective frequency or pulse width, respectively) was unchanged with VF and reduced with VP. This may suggest that the diabetic neuron release less transmitter (VF), which can be compensated for by the activation of less sensitive neurons (VP). Actually, the uptake of 3H-noradrenaline into the (4 weeks-) diabetic vas was normal but the stimulation-induced fractional release of tritium was decreased by 26%. It is concluded that a sympathetic neuropathy occurred in the vas deferens of the streptozotocin-diabetic mouse.
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PMID:The field-stimulated vas deferens of the streptozotocin-diabetic mouse: effects of prazosin, alpha, beta-methylene ATP, and variation of stimulation parameters. 276 Jun 3


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