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

A newly developed alpha 2 blocker, midaglizole (DG-5128, 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate) has been shown to have a hypoglycemic action in healthy controls as well as in diabetics. Since human platelets are rich in alpha 2 receptors, the effects of midaglizole on platelet aggregation were investigated. In normal controls, ADP- or epinephrine-induced platelet aggregation was significantly inhibited 2 h after oral administration of 300 mg midaglizole. Midaglizole also suppressed diabetic platelet aggregation stimulated by 10 or 100 microM epinephrine and delayed the initiation of collagen-induced aggregation at 30 micrograms/ml. In vitro addition of midaglizole at 9 or 90 microM significantly inhibited epinephrine-induced platelet aggregation. Furthermore, long-term administration of midaglizole suppressed diabetic platelet aggregation induced by 0.5-1 microM ADP or 1 microM epinephrine. These results suggest that alpha 2 blockade not only blunts diabetic epinephrine-induced platelet aggregation but also affects ADP- or collagen-stimulated platelet aggregation, indicating that this alpha 2 blocker may offer a new approach to the treatment of diabetic microangiopathy.
Diabetes Res Clin Pract 1989 Sep 18
PMID:A new hypoglycemic agent, midaglizole, blunts diabetic platelet aggregation: a possible role of alpha 2 blockade. 257 25

In vitro platelet aggregometry with epinephrine, adenosine-diphosphate, collagen and arachidonic acid was performed in 201 patients with diabetes, and in 106 healthy subjects. Those patients who were free of nephropathy showed hyperaggregability to collagen and arachidonic acid, and also to epinephrine and adenosine diphosphate, when neuropathy occurred. Patients with nephropathy, both with and without azotaemia, had diminished platelet responses to each of the four aggregating agents as compared to age- and sex-matched controls. Aggregability was not dependent on type of diabetes. It is concluded that diabetic nephropathy is characterized by decreased in vitro reactivity of platelets. Further researches are necessary to explain in vitro hypoaggregability besides the numerous evidence of in vivo hyperfunction of platelets in diabetes.
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PMID:[Differences in platelet aggregation in various microangiopathic complications of diabetes mellitus]. 264 41

When tested in insulin-deficient animal models of diabetes, islet activating protein (IAP) has been shown to increase the secretion of insulin and to improve glucose intolerance. The genetically obese fa/fa rat is an animal model of impaired oral glucose tolerance that does not have reduced insulin secretion. In this model IAP treatment increases basal insulin levels, resulting in lower basal glycemia. However, glucose tolerance following an oral glucose load was worsened by IAP. This was found to be due to an exaggerated stimulation of hepatic glucose production (HGP) following glucose, a defect that is already present in the absence of IAP. IAP has been reported to inhibit (by ADP ribosylation) the inhibitory regulatory protein (Ni) of adenylate cyclase. It is therefore suggested that the increased HGP following oral glucose in fa/fa rats either in the absence or in the presence of IAP treatment may result from a cAMP-mediated mechanism. A beta adrenergic activation or a stimulation of glucagon output could therefore be potential candidates responsible for glucose intolerance in obese fa/fa rats.
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PMID:The effects of islet activating protein on oral glucose tolerance in the genetically obese fa/fa rat. 265 21

In the present study the effects of a short term intensive glycaemic control obtained with subcutaneous insulin therapy on lipids and apoprotein levels, platelet aggregation, platelet sensitivity to prostacyclin and platelet thromboxane production were investigated in 20 patients with type 2 diabetes and vascular disease. In 11 out of the 20 patients there was a significant improvement of glycaemic control (fructosamine reduction). Only with tight improvement of glycaemic control there was significant change in the concentration of ADP and collagen required to produce 50% of the maximum aggregation wave response, in the responsiveness of platelet to PGI2 and in the TxB2 synthesis. Lower Apo B levels were also shown in the tight control group suggesting that Apo B changes may have influenced platelet aggregation and thromboxane synthesis.
Diabetes Res 1989 Jan
PMID:Platelet function in patients with type 2 diabetes mellitus: the effect of glycaemic control. 266 42

The ATP- and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 mumol/l ATP (with 2 mM Mg2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATP-sensitive K-currents half-maximally at 18 mumol/l; the sensitivity to tolbutamide was somewhat less in the inside-out patch. Ca-activated K-channels were unaffected by tolbutamide (10 mmol/l). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.
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PMID:The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells. 267 93

The goal of the present study was to follow the clinical behaviour of 6 non diabetic patients (5 females and 1 male, aged 23-68) suffering from necrobiosis lipoidica. Thickening of the basalmembrane of capillaries could be confirmed by electron microscopy, although the histological structure of skin alterations are not different from those observed in diabetes mellitus. Three patients (2 females and one male) showed impaired glucose tolerance, 2 other patients had increased levels of total cholesterol, whereas one patient suffered from both metabolic disturbances. After treatment with ASA (acetylsalicylic acid, 1.0 g/day) and dipyridamole (200 mg/day) for six weeks, the decrease of platelet in vitro aggregation in platelet rich plasma could be observed by stimulation with arachidonic acid, epinephrine, ADP and collagen, respectively. Healing of the exulceration of skin lesion could be detected by the use of the combined treatment of ASA and dipyridamole in 4 cases.
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PMID:[Necrobiosis lipoidica without diabetes mellitus (diagnostic and therapeutic possibilities)]. 269 55

The role of metformin on platelet aggregation was studied in subjects affected by relatively well controlled type 1 diabetes. 1700 mg of metformin were added to their usual daily treatment; nothing else was changed. Patients were trained to monitor their own glycaemia and presence of degenerative retinopathy was proved. Before the administration of metformin and on day 21, the platelet induced by 1.25, 2.5 and 5 mumol of ADP and by collagen was studied. Fibrinogen, cholesterol, triglycerides, glycosylated haemoglobin and mean blood glucose levels did not show any significant modification after treatment but the maximum aggregation induced by ADP was significantly decreased; the inhibition of aggregation was particularly sensitive for low doses of ADP. No significant correlation was found between the variations in metabolism data and the reduction of the amplitude of platelet aggregation. Metformin, added to the usual treatment undergone by a diabetic treated with insulin, seems to affect platelet aggregation independently of other metabolic factors.
Diabetes Res Clin Pract 1989 Jan 03
PMID:Study of the effect of metformin on platelet aggregation in insulin-dependent diabetics. 270 18

For the metabolic characterization of immunocompetent cells which are involved in the development of an insulin-dependent diabetes, a method for measurement of adenine uptake by mononuclear and macrophage-depleted mononuclear cell populations and of incorporation rates into the ATP, ADP, AMP and hypoxanthine fractions of these cells is presented and examined for its informative value in a cross-sectional study of individuals at risk of developing insulin-dependent diabetes. Values of 30 controls were compared with those of 53 risk persons. In controls and in 28 of the risk persons the adenine uptake by mononuclear cells was two to three times higher than that by the macrophage-depleted mononuclear cell population, suggesting high adenine metabolic activity of phagocytic cells. This activity was significantly decreased in the phagocytic cells of the remaining 25 risk persons. Additionally, the adenine incorporation rates into the adenine nucleotides of mononuclear cells were reduced by approximately 50% in these 25 risk persons. The alterations of purine metabolism were found associated with clinical symptoms of transient alterations of glucose tolerance and in the case of manifestation with a mild (HLA DR 3) type of insulin-dependent diabetes.
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PMID:Alterations of purine metabolism in mononuclear cells of individuals at risk of developing type I (insulin-dependent) diabetes mellitus. 280 59

The aim of this study was to investigate the influence of insulin on platelet function, both in vitro and in vivo. For the in vitro investigation, we evaluated whether insulin affects platelet function at a physiological hormone concentration by incubating the platelet-rich plasma (PRP) of fasting subjects with human regular insulin at the final concentration of 40 microU/ml for 30 min; we observed a significant reduction of platelet sensitivity to all the aggregating agents employed, i.e., ADP, platelet-activating factor (PAF), epinephrine, collagen, and Na+ arachidonate. To investigate whether the insulin effect on platelets is dose dependent, we incubated the PRP of fasting subjects with different concentrations of human regular insulin (40, 80, 120, and 160 microU/ml) for 5 min, and we observed that the insulin-induced reduction of platelet sensitivity to aggregating agents is a dose-dependent phenomenon. Furthermore, the comparison between the platelet responses after 5 and 30 min of incubation with insulin showed that the insulin effect on platelet aggregation is time dependent. The lack of specificity of its inhibiting activity suggests that insulin does not interfere with the initial binding of each aggregating agent at specific sites but does influence a common step of platelet aggregation. Our study rules out the possibility that insulin reduces platelet-function-modifying intraplatelet cAMP levels or thromboxane A2 production, because this hormone decreases the platelet concentrations of cAMP--a phenomenon that, per se, promotes platelet aggregation--and does not modify collagen or Na+ arachidonate--induced platelet production of thromboxane A2, measured by radioimmunoassay of its stable-metabolite thromboxane B2.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Jun
PMID:Insulin directly reduces platelet sensitivity to aggregating agents. Studies in vitro and in vivo. 283 53

The discovery of a cold-labile cytosolic acetyl-CoA hydrolase of high activity in rat liver by Prass et al. [(1980) J. Biol. Chem. 255, 5215-5223] has questioned the importance of mitochondrial acetyl-CoA hydrolase for the formation of free acetate [Grigat et al. (1979) Biochem. J. 177, 71-79] under physiological conditions. Therefore this problem has been reevaluated by comparing various properties of the two enzymes. Cold-labile cytosolic acetyl-CoA hydrolase bands with an apparent Mr of 68000 during SDS/polyacrylamide gel electrophoresis, while the native enzyme elutes in two peaks with apparent Mr of 136000 and 245000 during gel chromatography in the presence of 2 mM ATP. The mitochondrial enzyme elutes under the same conditions with an apparent Mr of 157000. Under conditions where the cold-labile enzyme binds strongly to DEAE-Bio-Gel and ATP-agarose, the mitochondrial enzyme remains unbound. The cold-labile enzyme can be activated 14-fold by ATP, half-maximal activation occurring already at 40 microM ATP. AdoPP[NH]P, AdoPP[CH2]P and GTP have a similar though weaker effect. ADP as well as GDP can completely inhibit the cold-labile enzyme with 50% inhibition occurring for both nucleotides at about 1.45 microM. The binding of ATP and ADP is competitive. Acetyl phosphate and pyrophosphate have no effect on the activity of the cold-labile enzyme. The mitochondrial acetyl-CoA hydrolase is not affected by these nucleotides. CoASH is a strong product inhibitor (approximately equal to 80% inhibition at 40 microM CoASH) of the cold-labile enzyme, but only a weak inhibitor of the mitochondrial enzyme. Under in vivo conditions the activity of the cold-labile cytosolic acetyl-CoA hydrolase can be no more than 7% of the activity calculated for mitochondrial acetyl-CoA hydrolase under the same conditions. Accordingly the mitochondrial enzyme seems to be mainly responsible for the formation of free acetate by the intact liver, especially in view of the fact that the substrate specificity of the mitochondrial enzyme is much higher (activity ratios acetyl-CoA/butyryl-CoA 4.99 and 1.16 for the mitochondrial and the cold-labile enzyme respectively). Alloxan diabetes neither increased the activity of the cold-labile enzyme nor that of the mitochondrial enzyme. No experimental support has been found yet for the hypothesis that the acetyl-CoA hydrolase activity of the cold-labile enzyme represents the side-activity of an acetyl-transferase.
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PMID:On the regulation of cold-labile cytosolic and of mitochondrial acetyl-CoA hydrolase in rat liver. 285 46


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