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

The Ivanovas-Sieve (IVA-SIV) rat represents the only available animal model of endogenous hypertriglyceridemia, in the absence of obesity and/or overt diabetes. Since plasma lipids/lipoproteins can modulate platelet reactivity and eicosanoid metabolism, these were examined in two groups of Charles River (CR) and IVA-SIV rats of identical age. The IVA-SIV rats had 2-fold higher plasma triglycerides and a 55% higher number of circulating platelets; the number of platelets was significantly correlated with triglyceridemia. Platelet reactivity to ADP and to collagen was significantly reduced in these animals, whereas the formation of thromboxane B2 did not differ from that of the CR. After perfusion of platelet-rich plasma (PRP) through the aortas of animals of the two strains, platelet aggregability, already lower in the IVA-SIV, was reduced to a higher extent compared to the CR. Increased levels of the prostacyclin metabolite 6-keto-PGF1 alpha were identified in the perfusate from the aortas of IVA-SIV rats. Platelets from these animals also showed an increased sensitivity to Iloprost, a stable prostacyclin analogue, with an IC50 1.7-fold lower compared to CR rats. Spontaneous hypertriglyceridemia in the IVA-SIV model is not associated with platelet hyperresponsiveness, but rather with a reduced sensitivity to major aggregants.
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PMID:Reduced platelet aggregability and increased vascular prostacyclin formation in a variant rat strain (IVA-SIV) with endogenous hypertriglyceridemia. 321 76

It has been proposed that the development of diabetic complications may involve a depletion of cellular myo-inositol due to an increase in polyol (sorbitol) formation. We therefore initially examined the effect of diabetes on levels of these metabolites in isolated cerebral microvessels. Compared with microvessels from control rats, microvessels from diabetic animals showed no detectable alteration in myo-inositol levels and a small increase in sorbitol content. To assess whether myo-inositol depletion might occur in only certain microvascular cells, cultured bovine cerebral microvascular pericytes and endothelium were grown for 3 or 18-20 days at 1.1, 5.5, or 22.2 mmol/l glucose. Increased medium glucose concentration resulted in increased sorbitol content in both cell types after both periods of incubation (p less than 0.05). In contrast, a significant decrease in myo-inositol content (22%, p less than 0.01) was observed only in pericytes grown for 18-20 days in the high glucose medium. Neither the adenosine 5'-triphosphate content nor the adenosine 5'-triphosphate/adenosine 5'-diphosphate (ATP/ADP) ratio of the pericytes was affected by the medium glucose concentration, indicating that the decrease in myo-inositol was not caused by a deficiency in the cellular energy state affecting the active transport of myo-inositol. These data suggest that myo-inositol depletion occurs selectively in the pericyte, a cell type known to be the site of early morphological changes in diabetes. Furthermore, the depletion apparently requires prolonged exposure to high glucose and is not due to a change in energy state.
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PMID:Chronic exposure to high glucose decreases myo-inositol in cultured cerebral microvascular pericytes but not in endothelium. 324 Aug 40

We investigated triglycerides, total cholesterol, HDL cholesterol, the fatty acid patterns of serum triglycerides, cholesterol esters and phospholipids in relation to the ADP induced platelet aggregation in 34 long-term insulin-dependent diabetic patients with an extremely long diabetes duration of about 40 years. The concentrations of triglycerides, total cholesterol and HDL cholesterol of the patients did not differ from those of an age-matched non-diabetic control group. In the insulin-dependent diabetics the percentages of arachidonic and eicosapentaenoic acid in both serum cholesterol esters and phospholipids were decreased in comparison with control subjects. No difference was observed with respect to the ADP induced platelet aggregation between long-term diabetics and controls. The findings demonstrate that type I diabetic patients with an extremely long duration of diabetes are not characterized by increased serum lipids or platelet aggregation, both being well known risk factors for macroangiopathy. However the decreased portions in eicosanoid synthesis precursors may indicate a disturbed fatty acid metabolism.
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PMID:Relationship between fatty acid pattern and platelet aggregation in long-term insulin-dependent type I diabetics. 324 13

The results are presented of a controlled study in male Wistar rats into the effects of 24R,25-dihydroxyvitamin D3 on blood glucose levels, bone calcium content and ADP-induced platelet aggregation in streptozocin-induced diabetes mellitus. Blood glucose levels were shown to be decreased by 10 micrograms/kg 24R,25-dihydroxyvitamin D3. The reduced bone calcium content associated with diabetes mellitus was returned to normal levels with both 1 and 10 micrograms/kg 24R,25-dihydroxyvitamin D3. It was also shown to exhibit dose-dependent anti-platelet activity. The data suggest that 24R,25-dihydroxyvitamin D3 might have potential as a mild therapeutic agent in the treatment of osteoporosis and platelet hyperactivity associated with diabetes mellitus.
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PMID:Effect of 24R,25-dihydroxyvitamin D3 in experimental diabetic rats. 326 45

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

The development of insulin-dependent diabetes mellitus is thought to be dependent on either the autoimmunity or the interaction of environmental agents with the pancreatic beta cells, or both in a genetically susceptible host. As environmental factors affecting the induction of type I diabetes, diabetogenic chemicals and viruses are likely candidates as primary injurious agents for pancreatic beta cells in man and animal. A number of structurally diverse chemicals including alloxan, streptozotocin, chlorozotocin, vacor, and cyproheptadine are diabetogenic mainly in rodents and sometimes in man. The possible mechanisms for the beta cell destruction by these chemicals include (a) generation of oxygen free radicals and alteration of endogenous scavengers of these reactive species; (b) breakage of DNA and consequent increase in the activity of poly ADP ribose synthetase, and enzyme depleting NAD in beta cells; and (c) inhibition of active calcium transport and calmodulin-activated protein kinase activity. Regarding viruses, a number of different viruses including encephalomyocarditis virus, Mengovirus, Coxsackie B viruses, and Reoviruses can infect and destroy pancreatic beta cells mainly in rodents and sometimes in humans. In the murine model, the development of encephalomyocarditis and Coxsackie B virus-induced diabetes is dependent on the genetic background of the host and the genetic makeup of the virus. Mengo-2T virus has caused diabetes in strains of mice resistant to encephalomyocarditis virus-induced diabetes. In contrast to encephalomyocarditis virus, Coxsackie B viruses, and Mengovirus, reovirus type 1 seems to be somewhat associated with an autoimmune response in the induction of diabetes. In addition to the murine model, cotton rats become diabetic when inoculated with Mengovirus 2T. Furthermore, cumulative environmental insults with Coxsackie B viruses and chemicals result in diabetes in non-human primates. In man, there may be 2 possible roles for viruses in the pathogenesis of insulin-dependent diabetes mellitus. The one is acute cytolytic infection of beta cells (e.g., Coxsackie B viruses), which may sometimes induce diabetes in genetically predisposed individuals, and the other one is slow and persistent infection (e.g., congenital cytomegalovirus and Rubella), which may induce autoimmunity, leading to type I diabetes.
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PMID:Effects of environmental factors on the development of insulin-dependent diabetes mellitus. 331 67

ATP, ADP, phosphocreatine (PCr), creatine (Cr), glucose, malate, sorbitol, and myo-inositol (MI) were measured by quantitative histochemical techniques in pure neuroectodermal tissue of rat embryos of gestation days 11 and 12 that were dissected from normal and streptozocin-induced diabetic mothers. Neither gestational age nor maternal diabetes affected the tissue's energy potential (ATP-to-ADP and PCr-to-Cr ratios). Diabetes resulted in a fourfold rise in the embryonic glucose and a 25% increase in neuroectodermal malate content. Maternal hyperglycemia caused a rise in fetal sorbitol at days 11 and 12 of gestation. The MI content of the neuroectoderm was not affected by the maternal diabetic state in perfusion embryos (day 11); however, the near doubling of MI that occurs from day 11 to day 12 during normal development was prevented. Thus, embryos isolated from diabetic mothers on gestation day 12 had 30% less MI than embryos isolated from normal mothers. From these data we conclude that a rise in tissue sorbitol is not always accompanied by a fall in tissue MI. These results and recent information in the literature implicate involvement of decreased MI concentrations in the process leading to malformation of the nervous system in diabetic embryopathy.
Diabetes 1988 Jul
PMID:Diabetes affects sorbitol and myo-inositol levels of neuroectodermal tissue during embryogenesis in rat. 338 92

Erythrocytes, obtained from blood of 12 patients with diabetes mellitus and of 6 donors, were incubated in isotonic medium at 37 degrees within 180 min. Patterns of thiamin metabolism (activity of transketolase and TDP-effect), of glycolysis (content of glucose, lactate) and of energy metabolism (ATP, ADP, AMP and 2,3-DPG) were studied during the incubation. The ratios of energy-synthesizing and energy-consuming reactions were shifted towards the latter reactions in erythrocytes of the patients, which appears to be among the factors responsible for impairment of thiamin metabolism in diabetes. In order to correct the impairments found some drugs, such as insulin, thiamin, cocarboxylase, thiamin combined with adenine were added into the incubation medium. Insulin and cocarboxylase as well as insulin combined with thiamin and adenine exhibited the best effect on the patterns studied; these drugs normalized the vitamin B1 metabolism and improved the parameters of energy metabolism within 120 min of incubation in erythrocytes isolated from blood of patients with diabetes mellitus.
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PMID:[Relation between the changes in thiamine metabolism and energy processes in erythrocytes of patients with diabetes mellitus and approaches to their correction with drugs]. 352 86

D-Glucose increased the cytosolic NADH/NAD+ ratio (but not the cytosolic NADPH/NADP+ ratio), augmented O2 uptake, raised the ATP/ADP ratio, decreased 86Rb outflow, and stimulated insulin release in tumoral insulin-producing cells of the RINm5F line. L-Leucine and 4-methyl-2-oxopentanoate also stimulated insulin secretion. In the RINm5F cells, as in normal islet cells, the nonmetabolized analogue of L-leucine, 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), activated glutamate dehydrogenase, augmented L-[U-14C]glutamine oxidation, and induced a more reduced state of cytosolic redox couples. However, in sharp contrast to either its effect in normal islet cells or that of D-glucose in the tumoral cells, BCH severely decreased O2 uptake, lowered the ATP/ADP ratio, increased 86Rb outflow, and inhibited insulin release in the RINm5F cells. These findings are interpreted to support the concept that the rate of ATP generation represents an essential determinant of the secretory response of insulin-producing cells to nutrient secretagogues.
Diabetes 1987 Feb
PMID:Opposite effects of D-glucose and a nonmetabolized analogue of L-leucine on respiration and secretion in insulin-producing tumoral cells (RINm5F). 354 45

Normal platelet sensitivity to in vitro ADP-induced aggregation (median 46, range 32-62% dT) and a normal antiaggregatory effect of prostacyclin (PGI2; ID50:0.65, range 0.18-2 ng PGI2/ml PRP) were found in a carefully selected group of 30 fairly well-controlled (average HbA1c 7.0%) Type 1 diabetic patients (14m/16f; median age 27.5, range 15-45 yr; duration of disease 7, range 1-24 yr) without macroangiopathy in comparison to 19 (9m/10f; age 26, range 17-40 yr) closely matched healthy controls (42, range 34-63% dT; 0.55, range 0.35-1 ng PGI2/ml PRP). By contrast, platelet malondialdehyde (MDA) release was significantly (p less than 0.001; Mann-Whitney, two-tailed, non-parametric test) increased in diabetics (6.55, range 0.91-18.94 nmol/10(9) platelets) in comparison to controls (3.9 range 2.6-6.9 nmol/10(9) platelets). Since MDA has been used as an indicator of platelet thromboxane formation (a potent stimulator of platelet aggregation), elevated platelet MDA in diabetics has been attributed to platelet activation. In the present study, for the first time increased platelet MDA release in diabetics has been shown to occur independently from enhanced platelet aggregation, even in well-controlled patients without evidence of either macroangiopathy or microangiopathy. This could be of clinical importance, since MDA is known to act on low density lipoprotein-uptake of human macrophages.
Diabetes Res 1986 Oct
PMID:Increased platelet malondialdehyde, but normal platelet sensitivity to adenosine-5-diphosphate and prostacyclin in well-controlled type 1 diabetics without vascular complications. 354 22


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