Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet activity is increased in persons with insulin dependent diabetes mellitus (IDDM). Receptor-medicated phospholipase C (PLC) activation and hydrolysis of phosphatidylinositol bisphosphate (PIP2) accompanies platelet activation. Previous work from our laboratory has shown that PIP2 hydrolysis is decreased in platelets of persons with IDDM. PIP2 hydrolysis is mediated via a phosphoinositide(PI)-specific PLC. PI-PLC activity is regulated by guanine nucleotide(GTP)-binding proteins. We therefore examined the hypothesis that platelet aggregations and PI turnover in platelet from subjects with IDDM is linked to alterations in PI-specific PLC activity. We found thrombin induced platelet aggregation was increased in the IDDM group. Basal PI and PIP2-specific PLC activity was not statistically different for the two groups. Guanine-nucleotide stimulated PIP2-specific PLC activity was decreased in the IDDM platelets. The mechanism for the reduced PLC activity and its role in the platelet hyperaggregation requires further study.
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PMID:Reduced guanine nucleotide-stimulated polyphosphoinositide specific phospholipase C in platelet hyperaggregation in IDDM. 131 91

Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications.
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PMID:Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus. 144 May 30

The aim of this study was to evaluate the balance between thrombin and plasmin activity in a group of 79 diabetic patients (IDDM and NIDDM). For this purpose we determined fibrinopeptide A (FPA) and B beta 15-42, specific products of thrombin and plasmin activity. Moreover we investigated the behaviour of antithrombin III and alpha 2 antiplasmin, important inhibitors of blood coagulation and fibrinolysis. Results show an increase both in FPA and B beta 15-42 in IDDM and NIDDM patients when compared to healthy controls. However the ratio between B beta 15-42 and FPA was lower than in controls indicating an imbalance between thrombin and plasmin activity. Antithrombin III levels were not different from the controls and no correlation was found with Hb A1c. alpha 2 antiplasmin was found to be higher in IDDM when compared both with NIDDM and controls. A non linear correlation was found between Hb A1c and alpha 2 AP in both diabetic groups. We conclude that the imbalance between thrombin and plasmin activity may have a role in determining fibrin deposition. These subclinical abnormalities, unrelated to vascular complications and duration of the disease, may progressively contribute to the development of the vascular complications in diabetes.
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PMID:Is the imbalance between thrombin and plasmin activity in diabetes related to the behaviour of antiplasmin activity? 169 51

Platelet function (as production of thromboxane B2 by platelets stimulated with collagen, and plasma beta-thromboglobulin) and thrombin activity (as plasma fibrinopeptide A) were investigated in eight young (mean age 27 +/- 3 SE years) male patients in which type 1 diabetes mellitus had been diagnosed 2 to 6 months previously. They were all in excellent stable metabolic control (mean HbA1c 5.6 +/- 0.4 SE %) and free from any complications. The haemostatic variables were assessed at rest and after cycloergometric exercise to exhaustion. When compared to age- and sex-matched healthy controls, patients showed higher beta-thromboglobulin, fibrinopeptide A and thromboxane B2 at rest. After exercise, plasma beta-TG increased only in the controls. Platelet and thrombin activation are present in the very early stages of type 1 diabetes mellitus, in the absence of any complications.
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PMID:Primary platelet activation in recent-onset type 1 diabetes mellitus. 214 55

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.
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PMID:Platelet and clotting activities after cold stress in diabetic patients. 297 Jun 90

The fibrinolytic resistance of platelet-rich arterial thrombi received much attention. Clot lysis method was used to assess the in vitro fibrinolytic properties in diabetes mellitus. Platelet rich (PRP) clots were formed by addition of thrombin, and lysis was induced by tissue-plasminogen-activator. The coagulation and lysis was followed by the light scattering properties. A special pattern of good initial lysis followed by a second clotting phase was observed in more than half of insulin dependent diabetic patients, while a similar pattern of clot-lysis was only occasionally found in non-insulin dependent diabetes mellitus or in the healthy control group. Following the thrombin activation of washed, gel-filtered platelets, the supernatants possessed an inhibitory action on in vitro lysis of PPP-clots. This suppression was remarkably stronger in IDDM, along with the highest PAI-1 activity concentration ratio of the platelet lysates, compared to plasmatic levels. The relation of this special type of PRP clot-lysis resistance to diabetic vascular complications needs further clarifying and investigations.
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PMID:Altered lysis resistance of platelet-rich clots in patients with insulin-dependent diabetes mellitus. 749 4

The effect of insulin-induced hypoglycaemia on plasma coagulant activity was studied in 11 subjects with well-controlled, uncomplicated type 1 diabetes. Thrombin generation was determined in plasma by a computer ex-vivo assisted chromogenic method and by the activated partial thromboplastin time (APTT). In addition, factor VIII:C, thrombin-antithrombin III (TAT) complex and fibrinopeptide A (FPA) levels were measured. Hypoglycaemia induced a rise in mean (SD) factor VIII:C concentrations from a baseline level of 1.13 (0.32) IU/ml to a peak 15 min after onset of symptoms and they remained increased at 90 min [1.54 (0.57) and 1.5 (0.54) IU/ml, p < 0.001 respectively]. A corresponding reduction in time to generate 50% maximal thrombin activity occurred from a pre-insulin value of 56 (6) s to a minimum reading of 46 (7) s at 15 min (p < 0.001) and remained low at 90 min [48 (6) s, p < 0.001]. APTT shortened from 43.3 (4.8) s to 40.1 (4.6) s at 30 min (p < 0.001) but did not fall below the normal range (37.6-42.7 s) and no significant changes in TAT or FPA levels were noted. Factor VIII:C correlated inversely with time to generate 50% maximal thrombin activity and APTT (r = -0.580, p < 0.001; r = -0.673, p < 0.001, n = 66, respectively). The results show that the rise in plasma factor VIII:C levels induced by hypoglycaemia is accompanied by accelerated rates of generation of thrombin in contact-activated plasma, though concentrations of FPA and TAT remain unchanged, although TAT complexes are not a sensitive marker of in vivo thrombin generation.
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PMID:The effect of insulin-induced hypoglycaemia on factor VIII:C concentrations and thrombin activity in subjects with type 1 (insulin-dependent) diabetes. 779 37

We examined the hypothesis that hyperaggregating platelets from patients with insulin dependent diabetes mellitus (IDDM) have an alteration in location and function of the guanine nucleotide (GTP)-binding proteins. Platelets from 10 IDDM and 12 age-matched healthy control subjects were collected and washed. Thrombin-induced platelet aggregation (0.025 and 0.05 units for 60 seconds) was increased in IDDM (8.3 +/- 1.8% vs 22.3 +/- 4.4%, P < .05 and 49.9 +/- 7.3% vs 70.9 +/- 7.0%, P < .05). Four small molecular weight GTP-binding proteins were identified by binding of [32P]-GTP on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the cytosol and membranes of these platelets. Each showed specificity for binding [32P]-GTP by competitive inhibition with unlabeled GTP. The total of the 27/28 kDa proteins was decreased in the membrane fraction (414 +/- 30 vs 252 +/- 40 dpm micrograms-1 protein x min, P < .05) and increased in the cytosolic fraction (62 +/- 8 vs 129 +/- 21 dpm unit-1 LDH x min, P < .05) in IDDM. The 21 kDa protein (60.3 +/- 3.5 vs 45.4 +/- 2.9 dpm micrograms-1 protein x min, P < .05) was decreased in platelet membrane in persons with IDDM. In conclusion, increased platelet aggregation in IDDM is accompanied by an altered cellular distribution of a 27/28 kDa GTP-binding protein. These data suggest that the low molecular weight GTP-binding proteins of the 27/28 kDa range may play an important regulatory role in the hyperaggregatory platelets in diabetes.
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PMID:Low molecular weight GTP-binding proteins are altered in platelet hyperaggregation in IDDM. 842 53

We examined the role of coagulation-fibrinolysis system in Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). The degree of fibrin deposition around the vessels in the spinal cord was significantly higher in susceptible SJL/J mice on 30 days post intracerebral injection (i.c.) than resistant C57BL/6 mice on 30 days post i.c. or mock infected SJL/J mice. Treatment with batroxobin (30 BU/kg/day), which is a thrombin-like defibrinogenating enzyme, causing a profound degree of afibrinogenemia, suppressed clinical signs of TMEV-IDD. Plasma fibrinogen concentration was significantly decreased in batroxobin-treated mice. Histologically, though the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in batroxobin-treated mice compared to saline-treated control mice, fibrin deposition was markedly suppressed in batroxobin-treated mice. These findings suggest that batroxobin suppresses TMEV-IDD through its defibrination effect, and provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of the blood-brain barrier (BBB), are prerequisite events for clinical manifestations of TMEV-IDD.
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PMID:Fibrin deposition in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease. 925 49

Intracellular calcium ([Ca2+]i) and phorbol ester binding were studied in intact platelets of young patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Our objective was to evaluate disturbances in calcium regulation and signal transduction in platelets of diabetics. [Ca2+]i in platelets of the IDDM group (135 +/- 20 nmol/L) under basal conditions was significantly higher than that of the control group (81 +/- 8 nmol/L, P = .019), whereas at 60 seconds after stimulation with 0.1 National Institutes of Health (NIH) U/mL thrombin, [Ca2+]i in the NIDDM group (484 +/- 36 nmol/L) was significantly higher than that of the controls (347 +/- 22 nmol/L, P = .003) and IDDM group (360 +/- 45 nmol/L, P = .04), respectively. Phorbol 12,13-dibutyrate (PdBu) maximal binding capacity (Bmax) in the IDDM group was significantly lower than that in the control group either under basal conditions or after stimulation with thrombin (P = .0034 and P = .015, respectively). Bmax in the NIDDM group was significantly lower than that in the controls only after stimulation with thrombin (P = .047). The Kd for PdBu of the IDDM group was lower than that of the control group under basal conditions (P = .017). When analyzing the pooled data of all subjects, a significant correlation was observed between Bmax and Kd (under basal conditions, r = .544, P < .0001; after stimulation, r = .601, P < .0001). Our results support the idea that the increased affinity for PdBu may compensate for the decreased binding capacity. We interpret the data as indicating that the change in the binding of phorbol ester to protein kinase C (PKC) units may result in an altered PKC/calcium interaction in the pathogenesis of diabetes mellitus. Our study indicates that such metabolic derangements of [Ca2+]i have already been developing in young diabetic patients.
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PMID:Increased intracellular calcium and altered phorbol dibutyrate binding to intact platelets in young subjects with insulin-dependent and non-insulin-dependent diabetes mellitus. 925 80


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