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

The subcellular distribution of Mg2+-dependent phosphatidate phosphohydrolase in rat adipocytes between a soluble and a membrane-bound fraction was measured by using both centrifugal fractionation and a novel Millipore-filtration method. The relative proportion of the phosphohydrolase associated with the particulate fraction was increased on incubation of cells with noradrenaline or palmitate. Insulin on its own decreased the proportion of the phosphohydrolase that was particulate and abolished the effect of noradrenaline, but not that of palmitate. The effect of noradrenaline on phosphohydrolase distribution was rapid, the effect being maximal within 10 min. Noradrenaline exerted this effect with a similar concentration-dependence to its lipolytic effect. Inclusion of albumin in homogenization buffers decreased the proportion of the phosphohydrolase that was particulate, but did not abolish the effect of noradrenaline. There was limited correlation between the proportion of the phosphohydrolase that was particulate and the measured rate of triacylglycerol synthesis in adipocytes incubated under a variety of conditions. Starvation, streptozotocin-diabetes and hypothyroidism decreased the specific activities of the phosphohydrolase and glycerolphosphate acyltransferase in homogenates from epididymal fat-pads. Restoration of these activities in the diabetic state was seen after administration of insulin over 2 days or, in the short term, within 2 h after a single administration of insulin. Administration of thyroxine over 3 days caused restoration of these activities in the hypothyroid state. Starvation and diabetes increased the proportion of the phosphohydrolase found in the microsomal fraction. This change was not seen when albumin was present in homogenization buffers. The possible role of fatty acids as regulators of the intracellular translocation of the phosphohydrolase, together with the role of this enzyme in the regulation of triacylglycerol synthesis in adipose tissue, is discussed.
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PMID:Adipose-tissue Mg2+-dependent phosphatidate phosphohydrolase. Control of activity and subcellular distribution in vitro and in vivo. 302 68

Noradrenaline and isoproterenol kinetics using intravenous infusion of L-3H-NA and of 3H-isoproterenol were investigated in eight Type 1 (insulin-dependent) diabetic patients without neuropathy and in eight Type 1 diabetic patients with autonomic neuropathy matched for age, sex and duration of diabetes. Resting plasma noradrenaline and adrenaline concentrations were reduced in patients with autonomic failure (p less than 0.05). The metabolic clearance rate of noradrenaline was similar in both groups of patients, and the appearance rate of noradrenaline in plasma was reduced in patients with autonomic failure (p less than 0.01). The disappearance of L-3H-noradrenaline from plasma after the infusion of L-3H-noradrenaline had been stopped was not different in patients with and without neuropathy. The metabolic clearance of isoproterenol was not influenced by the presence of autonomic failure and mean values were similar to the corresponding values for noradrenaline. Isoproterenol was only taken up by a non-neuronal uptake; this finding may indicate that neuronal uptake is not important for the inactivation of circulating catecholamines. Alternatively, because the non-neuronal uptake of isoproterenol is probably greater than that of noradrenaline, we cannot exclude the possibility that a small decrease in the neuronal uptake of noradrenaline was compensated for by a slightly higher non-neuronal uptake.
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PMID:Noradrenaline and isoproterenol kinetics in diabetic patients with and without autonomic neuropathy. 302 92

Noradrenaline responses following 10 mg intravenous edrophonium were assessed in 32 insulin-treated diabetic men, allocated to 4 groups according to their responses to 5 cardiovascular autonomic tests. The group with the most severe autonomic involvement had no rise in plasma noradrenaline, in contrast to the other 3 groups, whereas the heart rate fell in all 4 groups. There were significant correlations between individual noradrenaline responses, cardiovascular reflex tests, 24 hour heart rate variation and pupil cycle time, depending on whether predominantly parasympathetic or sympathetic pathways or both were involved. These results indicate that the noradrenaline response to edrophonium cannot be used as a test of early sympathetic dysfunction in diabetics; and that autonomic nervous system involvement occurs simultaneously in different body systems.
Diabetes Res 1987 Dec
PMID:Noradrenaline response to edrophonium (Tensilon) and its relation to other autonomic tests in diabetic subjects. 344 10

This study was designed to examine the influence of physical training on the norepinephrine turnover rate in heart, pancreas, liver, and gastrocnemius muscles of normal and diabetic male rats at rest. Diabetes was induced with the IV injection of streptozotocin (45 mg/kg) and physical training was done on a treadmill according to a ten-week program. Norepinephrine turnover rate of tissues was estimated by following over time the decay in the specific activity of norepinephrine after a single IV bolus of tritiated norepinephrine (30 microCi/kg). Plasma glucose, insulin, and glucagon levels were also measured at the time of death. Although training caused a reduction in the plasma glucose values of diabetic rats, no changes in norepinephrine turnover rate were observed after the conditioning program. On the other hand, diabetes was associated with a significant 30% to 40% decrease in the pancreatic norepinephrine turnover rate. It is concluded that the beneficial effects of physical training on diabetes mellitus cannot be explained by adaptive changes in the sympathetic nervous system activity and that further work will be necessary to elucidate the mechanism whereby streptozotocin diabetes diminishes the pancreatic norepinephrine turnover.
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PMID:Effect of physical training on norepinephrine turnover in tissues of normal and diabetic rats. 351 Mar 61

Diabetes mellitus causes a cardiomyopathy in human subjects, independent of atherosclerotic coronary artery disease. Ventricular papillary muscle function studies in chronically diabetic rats and rabbits have shown diminished contractility and a prolonged duration of contraction. In rats there was complete reversibility of these changes with insulin therapy. However, the effects of insulin on the myocardial mechanics of diabetic rabbits have not been studied. Therefore, rabbits diabetic for 3-4 mo (after alloxan injection) were treated with PZI insulin for 3-4 mo, and the mechanical performance of their right ventricular papillary muscles was compared with that of untreated diabetic animals and age-matched controls. Insulin therapy normalized serum glucose concentration. All abnormalities in papillary muscle function were completely reversed in insulin-treated animals. Norepinephrine (NE) dose responses were also evaluated in muscles from all groups. There were no differences in the positive inotropic effects of NE between groups. However, the data suggested, in diabetic animals a blunted response of peak relaxation rate to NE; this abnormality was reversed in muscles from treated animals. These findings indicate that previous work on diabetic rats can be extended to diabetic rabbits and suggest that chronic insulin therapy completely reverses the contractile alterations in hearts from these diabetic animals.
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PMID:Reversibility of diabetic cardiomyopathy with insulin in rabbits. 351 May 67

Norepinephrine, isoproterenol, insulin, and glucagon increase the type II (low Km) iodothyronine 5'-deiodinase (5'-D) in the brown adipose tissue (BAT) of intact rats. Cycloheximide or actinomycin D blocks the increase after norepinephrine, suggesting new mRNA synthesis is required for this effect. The 3- to 10-fold increase in BAT 5'-D after insulin administration was also blocked by cycloheximide. The effects of all stimulators are blunted by fasting or streptozotocin-induced diabetes. While all these hormones have the potential for stimulating BAT 5'-D, the dose-response relationships suggest that norepinephrine and insulin are the most potent. These and our earlier studies showing additional effects of thyroid and growth hormones on BAT 5'-D point to the complex regulation of this enzyme, suggesting that the triiodothyronine produced from its action has an important role in the thermogenic response of this tissue.
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PMID:Hormonal regulation of iodothyronine 5'-deiodinase in rat brown adipose tissue. 353 96

Insulin-dependent diabetes mellitus (IDDM) in humans is accompanied by an attenuation of the response of glucagon to hypoglycemia. To identify an animal model of IDDM with alpha-cell unresponsiveness to glucopenia in which to pursue morphologic and in vitro functional investigation of the lesion, pancreases isolated from rats with IDDM induced by streptozocin (STZ) or occurring spontaneously in BB/W rats were perfused with buffer containing 150, 25, and 150 mg/dl of glucose. In both forms of IDDM the normal glucagon rise during glucopenia was markedly impaired, suggesting an abnormality comparable to that of human IDDM. Studies of the insular sympathetic apparatus were conducted in these rat models. Electron-microscopic examination of peri-insular nerve endings disclosed no discernible abnormality in either form of rat IDDM. However, morphometric analysis of contacts between [3H]norepinephrine-labeled sympathetic nerve terminals and alpha-cells in pancreases from STZ-induced diabetic (STZ-D) rats revealed a 65-70% reduction in direct contacts. An 80% reduction in the number of nerve endings (not labeled) in direct contact with alpha-cells was also noted in the BB/W diabetic rats. Norepinephrine reuptake, studied only in the STZ-D group, was not impaired. The availability of local endogenous norepinephrine to alpha-cells and their sensitivity to exogenous norepinephrine was determined by perfusing 2, 5, or 10 micrograms/ml of tyramine, a releaser of endogenous norepinephrine, and norepinephrine at a concentration that in pancreases from nondiabetic rats gave a quantitatively similar glucagon response.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Mar
PMID:Morphologic and functional changes in sympathetic nerve relationships with pancreatic alpha-cells after destruction of beta-cells in rats. 354 58

The effects on ketogenesis and lipolysis of a norepinephrine (0.04 microgram/kg-min), epinephrine (0.04 microgram/kg-min), or saline infusion were examined in the overnight-fasted, conscious dog. Plasma insulin and glucagon levels were maintained constant by means of a somatostatin infusion (0.8 microgram/kg-min) and intraportal replacement infusions of insulin and glucagon. In saline-infused dogs, plasma epinephrine (62 +/- 8 pg/ml), norepinephrine (92 +/- 29 pg/ml), blood glycerol (87 +/- 10 microM), and plasma nonesterified fatty acid (NEFA) (0.82 +/- 0.17 mM) levels did not change. Total blood ketone body levels tended to rise (62 +/- 10 to 83 +/- 11 microM) by 3 h as did total ketone body production (1.5 +/- 0.4 to 2.2 +/- 0.4 mumol/kg-min) over the same time interval. Norepinephrine infusion to produce plasma levels of 447 +/- 86 pg/ml caused a sustained 50% rise in glycerol levels (66 +/- 17 to 99 +/- 15 mumol/L, P less than 0.05) and 53% rise in nonesterified fatty acids (0.53 +/- 0.07 to 0.81 +/- 0.15 mumol/L, P less than 0.05). Total ketone body levels rose by 43% (51 +/- 8 to 73 +/- 10 mumol/L) and ketone body production rose by a similar proportion (1.5 +/- 0.2 to 2.2 +/- 0.3 mumol/kg-min), changes that did not differ significantly from control animals. A similar increment in plasma epinephrine levels (75 +/- 15 to 475 +/- 60 pg/ml) caused glycerol levels to rise by 82% (105 +/- 23 to 191 +/- 26 mumol/L) in 30 min, but this rise was not sustained and the level fell to 146 +/- 14 mumol/L by 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 May
PMID:Regulation of ketogenesis by epinephrine and norepinephrine in the overnight-fasted, conscious dog. 388 59

Mice were rendered diabetic with streptozotocin. After intervals of approximately 4 weeks and 6 months, the vascular responses of cerebral surface arterioles (pial arterioles) with mean internal diameters of 35-39 micrometers were determined and compared with those of control mice. Norepinephrine, serotonin, prostaglandin F2 alpha, and papaverine were used. Only one agent was tested in a given mouse, each agent being applied to the surface vessels of that mouse at three different doses. Statistically significant dose-response relationships were always observed, but with one exception, no differences were found between the contractile responses (norepinephrine, serotonin, prostaglandin F2 alpha) or the dilating responses (papaverine) in diabetic vs normal mice. The one exception involved responses to serotonin following 4-5 weeks of diabetes. Here diabetic responses were 10-18% less than those of control. Though significant statistically, the difference may nevertheless be a chance occurrence, and is in any case sufficiently small to be of doubtful biological meaning. The overall data indicate no effect of diabetes on the responses of the selected pial arterioles to norepinephrine, serotonin, PGF2 alpha, and papaverine.
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PMID:Microvascular responses of intermediate-size arterioles on the cerebral surface of diabetic mice. 659 85

The response to vasoactive agents of microvessels in situ and large arteries in vitro was compared in normal and alloxan-diabetic rats. Noradrenaline was equally effective in evoking a constrictor response of mesenteric microvessels in normal and diabetic animals. The constrictor response to a standard amount of noradrenaline in such vessels was fully antagonized by acetylcholine or papaverine, the minimum effective doses being equivalent in normal and diabetic animals. In contrast, the minimum doses of histamine or bradykinin, effective in normal animals, had to be increased about 20 fold to be active in diabetic animals. Increased osmolarity of extracellular fluid caused a significant and equivalent increase in latency of the vasoconstrictor response of microvessels to noradrenaline in normal and diabetic animals. Concentration-effect curves, constructed from the response of isolated aortae to noradrenaline, were similar in normal and diabetic animals, provided the endothelium was removed. Diabetes only affected preparations in which the endothelium was left intact. In these, the median effective concentrations of noradrenaline were greatly increased in comparison with normal values. Precontracted aortae from normal and diabetic animals were equally relaxed by acetylcholine and histamine, provided the endothelium was left intact. Loss of the relaxant response of the preparations in all groups of animals was observed following removal of endothelial cells. It is suggested that different mechanisms may be involved in the effects of vasodilator agents on large arteries in vitro or small vessels in situ. Histamine and bradykinin which are potent permeability-increasing factors, may antagonize the vasoconstrictor response of microvessels to noradrenaline through an action on endothelial cells with increased vascular permeability and temporary changes in composition of extracellular fluid. The reactive process of endothelial cells to permeability factors was affected by diabetes mellitus. However, the response of microvessels to acetylcholine and papaverine which are devoid of permeability-increasing properties, was not influenced by diabetes.
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PMID:Vascular reactivity in diabetes mellitus: role of the endothelial cell. 665 56


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