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

Significant increase in the activity of an acetyl-CoA hydrolase (ATP-stimulated, ADP-inhibited enzyme) in the supernatant fraction of rat liver was observed after 44-68 h of starvation (about 2-fold), and in the early stage of diabetes (about 1.6-fold), but not in the chronic stage of diabetes. The increased enzymatic activity in starved rats returned to the control level within 20 h when the animals were given laboratory chow, but not when they were given fat-free diet with a high carbohydrate content, and the enzyme activity was increased by the latter diet containing 1% thyroid powder. A single intraperitoneal injection of 3,3'5-triiodo-L-thyronine or 3,3',5,5'-tetraiodo-L-thyronine resulted in twice the normal enzyme activity two days later, and conversely 7 days after thyroidectomy, the enzyme activity was about 60% of the control level. A single subcutaneous injection of alpha-(p-chlorophenoxy)isobutyric acid, a hypolipidemic drug, doubled the enzyme activity in euthyroid rats, but not in thyroidectomized rats. Of the various tissues tested besides the liver, only the kidney had detectable ATP-stimulated and ADP-inhibited enzyme activity (5% of the activity in liver cytosol). The kidney enzyme had similar kinetic and immunochemical properties to the liver enzyme. Changes in the enzyme activity in the liver in various states were closely related to the amount of enzyme present, judging from results obtained by enzyme-linked immunosorbent assay. The physiological role of this enzyme (which hydrolyzes acetyl-CoA to acetate and CoASH) may be in maintenance of the cytosolic acetyl-CoA concentration and CoASH pool for both fatty acid synthesis and oxidation.
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PMID:Physiological changes in the activities of extramitochondrial acetyl-CoA hydrolase in the liver of rats under various metabolic conditions. 286 34

The goal of this study was to determine whether responses of cerebral arterioles to vasoactive substances released by platelets are altered during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin (50-60 mg/kg ip). Rats were characterized as diabetic by a blood glucose of greater than 300 mg/dl. Diameter of pial arterioles was measured during superfusion with ADP, serotonin, and the thromboxane analogue (U-46619), with the use of intravital microscopy in control (non-diabetic) and diabetic rats. ADP (10(-5)M) increased pial arteriolar diameter by 13 +/- 1% (mean +/- SE) in control rats and did not change diameter of arterioles in diabetic rats (1 +/- 1%). Serotonin (10(-5)M) increased diameter of cerebral arterioles by 9 +/- 1% in control rats and constricted arterioles by 5 +/- 2% in diabetic rats. Nitroglycerin produced similar dilatation of cerebral arterioles in control and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilatation. The thromboxane analogue U-46619 produced similar constriction of cerebral arterioles in control and diabetic rats. Thus endothelium-dependent dilatation of cerebral arterioles in response to ADP and serotonin is profoundly impaired in diabetic rats.
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PMID:Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus. 292 30

The addition of 3-aminobenzamide (a potent inhibitor of poly(ADP-ribose)synthetase) into the incubation medium, prevents streptozotocin-induced inhibition of glucose-stimulated insulin release from isolated islets [control 142 +/- 14 microU X islet-1 X h-1; streptozotocin (0.5 mg/ml) 31 +/- 8; 3-aminobenzamide (1.0 mg/ml) 96 +/- 11; streptozotocin plus 3-aminobenzamide 122 +/- 19]. In vivo, intraperitoneal 3-aminobenzamide 300 mg/kg body weight prevents the appearance of overt diabetes in streptozotocin-treated rats. These protective effects of 3-aminobenzamide are dose-dependent and are similar to those exerted by nicotinamide. Taking into account that poly ADP-ribosylation is involved in the repair of damaged DNA, the protection exerted by 3-aminobenzamide against the diabetogenic effect of streptozotocin strongly supports the view that this acute effect may be a major consequence of the activation of DNA repair mechanisms in islet cells.
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PMID:Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, against streptozotocin-induced diabetes. 293 87

The effect of dihomogammalinolenic acid (DHLA) administration on platelet aggregation and prostaglandin production, erythrocyte fatty acid composition and serum lipids was compared in healthy subjects and insulin-dependent diabetics (IDDs). In healthy subjects, DHLA caused a significant inhibition of ADP-induced platelet aggregation and an increase in platelet PGE1 release; IDDs did not show these changes. There were no differences, however, in platelet thromboxane A2 (TXA2) or PGE2 release between healthy subjects and IDDs before and after DHLA. Following DHLA, the arachidonic acid content of erythrocytes increased in healthy subjects; this increase was not observed in IDDs. DHLA induced a significant fall in serum non-esterified fatty acid concentrations in both groups without altering either cholesterol or triglyceride concentrations. These data show for the first time that IDD platelets may have a specific defect of PGE1 synthesis quite distinct from the delta 5- and delta 6-desaturase defects known to be associated with experimental diabetes; this defect may contribute to platelet hyper-aggregability in diabetes; and DHLA has a potent antilipolytic effect in vivo; and erythrocytes from IDDs may have a delta 6-desaturase defect.
Diabetes Res 1986 Jan
PMID:The effect of dihomogammalinolenic acid on platelet aggregation and prostaglandin release, erythrocyte membrane fatty acids and serum lipids: evidence for defects in PGE1 synthesis and delta 5-desaturase activity in insulin-dependent diabetics. 293 1

Seventeen patients with insulin-dependent diabetes mellitus, all below the age of 45 years, were studied. Five of them had retinopathy but no other micro- or macrovascular diabetic complications. None of them had any other concurrent disorder or were on any medication but insulin. The results were compared to those of 17 healthy volunteers of comparable age. There was no difference between the two groups in venous platelet counts, serum production of thromboxane B2 (TXB2), ADP-induced platelet aggregation or bleeding times. As compared to the controls, the diabetics had significantly elevated blood glucose and glycosylated hemoglobin values. The mean plasma values of beta-thromboglobulin, platelet factor 4 and TXB2 were significantly lower in the patients than in the controls. Thus, our results do not lend support to the current concept that platelet reactivity is enhanced in diabetes mellitus.
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PMID:Evaluation of platelet reactivity in diabetes mellitus. 293 25

Activation of the vascular-platelet link of the hemostasis system: an increase in platelet ADP-induced aggregation, the appearance of platelet aggregates in the vascular bed, an increase in the patients' plasma of beta-thromboglobulin concentration, thrombocytic factor 4, a decrease in antiaggregation activity of the vascular wall and sensitifity of patients' platelets to antiaggregation action of acetylsalicylic acid, was found in diabetes mellitus patients. In the authors' opinion, the above changes play a role in disorders of the microcirculation of the organs and tissues and development of complications in these patients.
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PMID:[Vascular-platelet link in the hemostatic system of diabetics]. 294 May 88

The aim of our study was to investigate the mechanisms involved in hypoglycemia-induced platelet activation. Sixteen healthy male subjects received a 60-min intravenous infusion of human regular insulin at the rate of 64 mU . m-2 . min-1: throughout 150 min, we serially measured plasma concentrations of glucose, insulin, and counterregulatory hormones; platelet sensitivity to ADP, thrombin and platelet-activating factor; plasma concentrations of platelet markers for specific proteins of in vivo release reaction (beta-thromboglobulin and platelet factor 4). Our study showed that insulin-induced hypoglycemia causes a significant increase in platelet sensitivity to aggregating agents in vitro and a platelet release reaction in vivo. Hypoglycemia-induced platelet activation was not correlated with plasma glucose concentrations at nadir and occurred before the increase of plasma growth hormone and cortisol. To further elucidate the mechanisms of hypoglycemia-induced platelet activation, we incubated in vitro platelet-rich plasma (PRP) of seven fasting healthy subjects with the same concentrations of insulin, epinephrine, glucagon, growth hormone, and cortisol measured in vivo during insulin-induced hypoglycemia. Only epinephrine was able to increase platelet sensitivity to aggregating agents. To investigate the role of alpha-adrenergic receptors in this phenomenon, we also studied four healthy subjects on another occasion, repeating the above-described insulin infusion together with intravenous infusion of phentolamine (-15 to +150 min), 5 mg over 2 min followed by 500 micrograms/min. alpha-Blockade was able to suppress hypoglycemia-induced increase of platelet sensitivity to aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Jul
PMID:Studies on mechanisms involved in hypoglycemia-induced platelet activation. 294 27

Specific thromboxane synthetase inhibition is associated with a significant fall in abnormal albumin excretion rate in insulin-dependent diabetics (IDDs). This may be due to an effect on haemostasis or changes in renal blood flow. We have studied the effect of a specific thromboxane synthetase inhibitor, UK-38,485, on coagulation parameters in 15 IDDs, at -8, 0, 8 and 16 weeks after double blind administration of drug or placebo. Serum thromboxane B2 fell in the drug group (695 +/- 205 vs 134 +/- 180 pg/ml, n = 7, p less than 0.001), but not in the placebo group (713 +/- 409 vs 614 +/- 178 pg/ml, n = 8). The drug group showed significant reduction in adrenaline primary maximum (24 +/- 7 vs 37 +/- 7%, p less than 0.05) and ADP maximum (71 +/- 14 vs 81 +/- 7%, p less than 0.05) aggregation not seen in the placebo group. Dilute whole blood clot lysis time was, however, increased in the drug group (7.1 +/- 1.6 vs 6.25 +/- 2.4 hr, p less than 0.05) and no effect was observed in either group on in vivo parameters of platelet aggregation (beta-thromboglobulin, platelet factor 4 and platelet micro-aggregates). We conclude that specific thromboxane synthetase inhibition is probably not associated with an overall improvement in haemostasis and the clinical effects observed cannot be explained on this basis.
Diabetes Res 1986 Sep
PMID:Specific thromboxane synthetase inhibition and haemostasis in insulin-dependent diabetics. 294 9

Serum levels of apolipoprotein B were measured, and investigations of the platelet function were carried out in 32 patients with insulin-dependent diabetes and in 34 healthy controls similar in age. Mean serum levels of apolipoprotein B were 1.51 g/l in the diabetic patients and 1.18 g/l in the control group, and this difference was significant. In the diabetic patients a secondary wave of aggregation was more easily induced by low concentrations of adenosine diphosphate or adrenaline. It was also possible to induce 50% of maximal aggregation by lower concentrations of adenosine diphosphate or arachidonic acid in these patients, and their number of circulating platelet aggregates increased. Plasma levels of beta-thromboglobulin and platelet factor 4 were raised and, in the presence of N-ethyl maleimide, platelets from diabetic patients produced significantly more malondialdehyde than those from normal controls. The relationship between increased serum levels of apolipoprotein B and platelet hyperreactivity may be more than accidental and should be studied further to elucidate its possible implication with platelet function and atherogenesis.
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PMID:Apolipoprotein B and platelet function in diabetes mellitus. 295 58

Glucose and beta-hydroxybutyrate metabolism were compared in isolated cerebral microvessels from chronically diabetic and hypoglycemic rats. As noted previously, glucose oxidation and conversion to lactate are diminished in rats with streptozotocin-induced diabetes. The decrease in glucose metabolism did not result from selective damage to diabetic vessels during isolation, since the ATP level and the ATP/ADP ratio were similar to those of nondiabetic rats, and O2 consumption was increased. In addition, cerebral microvessel oxidation of beta-hydroxybutyrate was enhanced by diabetes. By contrast, microvessels from rats made chronically hypoglycemic by insulinoma engrafting 30 days earlier had a more than twofold increase in glucose oxidation and conversion to lactate, whereas their oxidation of beta-hydroxybutyrate was diminished by 50%. Unlike the insulinoma rats, no consistent increase in glucose metabolism was observed in microvessels from rats made hypoglycemic either by acute insulin administration or by a 4-day infusion of insulin. These results indicate that diabetes, and under some circumstances chronic hypoglycemia, markedly alters fuel metabolism in the cerebral microvasculature.
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PMID:Effects of hypoglycemia and diabetes on fuel metabolism by rat brain microvessels. 296 87


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