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)

Twenty-nine IDDM patients with borderline hypertension were randomly allocated to placebo or nitrendipine treatment. Nitrendipine was given orally at a dosage of 20 mg once daily over 4 weeks. Stimulated platelet thromboxane formation at rest and after standardized, non exhausting exercise was measured by standard methods. In addition, plasma levels of platelet factor 4 and aggregation responses to collagen and ADP were determined. In the treatment group thromboxane formation after stimulation with collagen (0.3 and 1.0 micrograms/ml) and 1 mM arachidonic acid (AA) was reduced in the resting state. Exercise induced change of thromboxane synthesis in response to 1.0 micrograms/ml collagen was significantly lower as compared to placebo (p < 0.05). In parallel, PF4 plasma levels were significantly lowered (p < 0.05). Whole blood aggregation after collagen stimulation (1.0 micrograms/ml) was reduced after 4 weeks of nitrendipine treatment, but ADP (5 microM) induced aggregation was not. These effects of nitrendipine were not seen in platelet rich plasma. In conclusion long-term nitrendipine treatment may inhibit collagen dependent platelet activation in the blood of diabetic patients with borderline hypertension.
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PMID:Reduced platelet thromboxane formation after long-term administration of a dihydropyridine calcium channel blocker: a prospective, double-blind, placebo-controlled study with nitrendipine in borderline hypertensive patients with IDDM-type diabetes mellitus. 128 47

Iloprost is a chemically stable analogue of prostacyclin, with similar vasodilator and anti-platelet actions. Platelet sensitivity to the inhibitory action of Iloprost has been tested in vitro. Platelet-rich plasma from six healthy subjects and from six patients with type 1 diabetes mellitus was incubated with different concentrations of Iloprost, and then stimulated with ADP (at threshold aggregating concentration) and collagen 4 micrograms/ml. The half-maximal inhibitory concentration (IC50) of Iloprost was calculated and no differences were found between patients and controls. The results of this study suggest that diabetic patients without complications do not differ from healthy subjects in their platelet sensitivity to Iloprost.
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PMID:Platelet sensitivity in vitro to the prostacyclin analogue iloprost in diabetic patients. 248 Mar 23

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.
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PMID:Study of the effect of metformin on platelet aggregation in insulin-dependent diabetics. 270 18

It has been speculated that platelet activation may contribute to the evolution of vascular complications in patients with Type I diabetes mellitus. To address this hypothesis, we measured the plasma and urinary metabolites of thromboxane, presumably of platelet origin, and of prostacyclin, derived from endothelial cells, in addition to more conventional indexes of platelet function. Urinary excretion of the metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha did not differ between diabetics with or without retinopathy and nondiabetic controls. Furthermore, measurement of platelet granule constituents, the aggregation responses to ADP or arachidonic acid, and levels of serum thromboxane B2 failed to discriminate between the groups. The institution of tight diabetic control with multiple daily injections of insulin failed to alter either urinary metabolite excretion or plasma levels of 11-dehydro-thromboxane B2. Conversely, insulin-induced hypoglycemia failed to alter the concentrations of plasma or urinary thromboxane metabolites in nondiabetic volunteers, despite a mean 60-fold increase in plasma epinephrine. These studies suggest that platelet activation does not precede the development of microvascular complications in patients with Type I diabetes who lack clinical evidence of macrovascular disease and have normal renal function. Furthermore, it is unlikely that platelet activation due to intermittent hypoglycemia contributes to the reportedly accelerated development of retinopathy in such patients, when they are subject to tight diabetic control.
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PMID:Thromboxane biosynthesis and platelet function in type I diabetes mellitus. 329 13

Purified fish oil (MaxEpa, 10 g/day) treatment for six weeks increased consistently the content of eicosapentaenoic (20:5, n-3), docosapentaenoic (22:5, n-3) and docosahexaenoic acid (22:6, n-3) and decreased that of arachidonic acid (20:4, n-6) and other n-6 polyunsaturated C-20 fatty acids (PUFA) of platelets both in insulin dependent diabetic (IDDM) (n = 13) and healthy women (n = 7), but it had no effect on the number and aggregation of platelets or on plasma beta-thromboglobulin. Serum TxB2, produced by diabetic platelets was reduced, but the urine 6-keto PGF1 alpha excretion, believed to reflect prostacyclin (PGI2) production was normal in the diabetics. During the MaxEpa treatment the response of thromboxane B2 (TxB2) release to ADP was decreased in platelet-rich plasma in the healthy subjects. However, in diabetics the fish oil treatment resulted in increased TxB2 formation from exogenous arachidonic acid. The results demonstrate the dependence of platelets fatty acid composition on dietary sources and suggest that at least in the diabetic platelets the diminished arachidonic acid content could be compensated by an activation of enzymes of thromboxane B2 pathway.
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PMID:Effects of purified fish oil on platelet lipids and function in diabetic women. 359 18

Increased platelet reactivity has been suggested in the pathogenesis of both arteriosclerosis and diabetic microangiopathy. Therefore, platelet function and platelet enzyme activities were assessed in a large group of 357 diabetics (256 patients with IDDM, aged 16-49 and 101 patients with NIDDM, aged 50-78) and 163 matched controls, and related to photographically documented retinopathy (Rd) and to peripheral vascular disease (PVD) as well as to plasma levels of von Willebrand factor (VIII R:Ag) as an indicator of endothelial damage. Patients with IDDM had increased platelet aggregation (PA, expressed as microM ADP threshold concentration) before Rd was detectable in comparison to control subjects (P less than 0.01). PA was further increased in patients with advanced Rd (P less than 0.01), whereas 20 newly diagnosed diabetics with IDDM exhibited normal PA. Patients with minimal Rd did not differ from patients without Rd. Plasma beta-thromboglobulin (reflecting platelet consumption in vivo) was enhanced significantly in patients with Rd only (P less than 0.05), as was malondialdehyde (MDA) production of platelets (as a measure of platelet endoperoxide formation). Factor VIII-related antigen in plasma was already increased in patients without Rd (P less than 0.05), yet more so in patients with Rd (P less than 0.01). Prostacyclin-stimulated adenylate cyclase activity (ACA) of platelets (as an antiaggregatory enzyme system) was twice as high in diabetics with advanced Rd compared with patients without Rd and with controls (P less than 0.01). Significant correlations were found between PA and plasma F VIII R: Hg, MDA production, and ACA of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet enzyme activities in diabetes mellitus in relation to endothelial damage. 608 25

A decreased insulin response, preferentially to glucose, has been considered a hallmark of non-insulin dependent diabetes mellitus (Type 2) in humans. Syndromes resembling human diabetes occur spontaneously in many animal species and can also be induced by treating animals with drugs or viruses, excising their pancreases or manipulating their diet. Among these models, rat diabetes induced by neonatal streptozotocin administration (n-STZ models) has been first recognized as an adequate tool to study the long-term consequences of a gradually reduced beta-cell mass. More recently, the GK (Goto Kakisaki) Wistar rat has become available and is now considered as a promising spontaneous rat model of non-insulin dependent diabetes. We and others have found that defects in insulin secretion and action develop in the n-STZ and the GK models, which in many ways resemble those described in human non-insulin dependent diabetes. This review is aimed to sum up with a comparative approach, the informations so far collected in the n-STZ and GK models concerning the cellular mechanisms leading to the desensitization of their beta-cells to glucose. Taken together, the data reinforce the view that the impairment of glucose-induced insulin release in n-STZ and GK rats is clearly related to a defect in oxidative glycolysis. This leads to a severe decrease in the mitochondrial oxidative catabolism of glucose-derived pyruvate. Its coincides with a lower ATP/ADP ratio in glucose-stimulated islets and a subsequent alteration of ionic events tightly coupled to the fuel function of the hexose in islet cells, i.e. the decrease in K+ conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose refractoriness of pancreatic beta-cells in rat models of non-insulin dependent diabetes. 780 48

A 26-year-old female with severe complications from type I diabetes mellitus of 17 years' duration (proliferative retinopathy, nephropathy with renal failure and nephrotic syndrome) developed rapid deterioration of vision in the right eye to 6/60 over a period of several weeks. There were no other neurological signs. Ophthalmological examination showed no worsening of the diabetic retinopathy, but the presence of bilateral optic atrophy, confirmed by visual evoked potentials. CT scan did not reveal any retrobulbar process, and MR scans of both the optic nerves and the visual pathways were unremarkable. The clinical features and the investigations pointed towards ischaemic optic atrophy. Detailed platelet studies showed intravascular platelet activation and an ADP-inducible increase in aggregation, although thromboxane formation was almost absent because of cyclooxygenase inhibition by acetylsalicylic acid. These findings suggest that the ischaemia was due to microcirculatory disturbances secondary to diabetic microangiopathy and platelet hyperreactivity.
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PMID:[Optic neuropathy in type-1 diabetes and acetylsalicylic acid-refractory thrombocyte activation]. 844 10

The answer to the question posed by the title (is there a relationship between aberrant Art gene expression and IDDM pathogenesis in NOD mice?) remains elusive. Conclusions are currently based almost entirely upon analysis of mRNA transcript levels rather than on T-cell-specific mono-ADP ribosylation activities. Our unpublished data, as well as data published in abstract form by Dr. L. Chatenoud and colleagues (48) indicate that gene transcription is not impaired in splenic leukocytes of older NOD mice, including those with spontaneous IDDM development. Based upon the limited data showing that there may be reduced expression of Art gene products in the earliest T cell immigrants from the NOD thymus, one would have to surmise that If there is a regulatory defect, it may be in allowing single positive thymic T cells to emigrate before they are fully mature. Therefore, development of anti-Art monoclonal antibody together with further studies regarding functions of mono(ADP-ribosyl)transferase in immunoregulation of different subpopulation of T-cells, may finally resolve the role that altered mono(ADP-ribosyl)transferase activities play in the pathogenesis of IDDM in NOD mice.
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PMID:Mono(ADP-ribosyl)transferase genes and diabetes in NOD mice. Is there a relationship? 919 57

Treatment with high doses of nicotinamide (niacinamide, vitamin B3) prevents or delays insulin-deficient diabetes in several animal models of type 1 diabetes and protects islet cells against cytotoxic actions in vitro. In recent-onset type 1 diabetes, nicotinamide administration improves beta-cell function, without significantly decreased insulin requirements. This review discusses the possible mechanism of action of nicotinamide in vivo. It is proposed that the key target of nicotinamide is the poly(ADP-ribose)polymerase (PARP), and to a lesser extent (mono)ADP-ribosyl transferases (ADPRTs). Suppression of PARP activity by nicotinamide not only decreases consumption of NAD+, the substrate of PARP, but also has major regulatory effects on gene expression, as shown for the major histocompatibility complex class II gene. In addition, PARP activity controls early steps of apoptosis. The possible suppression of ADPRTs by nicotinamide would also affect CD38, a membrane-bound external ADP-ribosyl transferase with potent immunoregulatory properties. Taken together, it is proposed that high doses of nicotinamide primarily affect ADP-ribosylation reactions in beta-cells as well as in immune cells and the endothelium. As a consequence, cell death pathways and gene expression patterns are modified, leading to improved beta-cell survival and an altered immunoregulatory balance.
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PMID:Nicotinamide in type 1 diabetes. Mechanism of action revisited. 1009 94


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