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

Tests were carried out on the influence of alloxan-induced diabetes mellitus on the metabolism and the ultrastructure of ovaries of juvenile rats. The diabetes mellitus caused the following changes in the metabolism: reduction in the concentration of ATP and NADPH, increase in the lactate/pyruvate quotient to above 40, reduction in the ATP/ADP quotient to below 1, reduction in the level of activity of the hydrogen-conveying enzymes G-6-P-dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase, increase in the level of activity of the alkaline phosphatase, reduction of the protein content. Ultrastructure: almost complete disappearance of the rough endoplasmic reticulum, shrinkage of the mitochondria, reduction of the cristae and condensation of the matrix. The smooth endoplasmic reticulum remains unchanged, the extent of the Golgi-complex is reduced. Easy removal of the lipid deposits.
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PMID:Metabolism and ultrastructure in ovaries of alloxan-diabetic juvenile rats. 0 67

Platelets from diabetic patients show both increased platelet adhesiveness and sensitivity to aggregating agents. Plasma levels of the platelet-active von Willebrand Factor and the closely related factor-VIII antigen are significantly elevated, while factor VIII procoagulant activity is not. This may reflect either intravascular coagulation or disproportionate production or degradation. Plasma factors that enhance ADP-induced platelet aggregation are found in 50% of unselected male diabetics. Activity is clearly demonstrated only when plasma is added immediately prior to adding subthreshold doses of ADP to platelet-rich plasma obtained from control subjects. Systematic investigations of the molecular nature of such factors and their interactions with platelets are in progress. In platelets obtained from diabetic subjects, we have previously found increased sensitivity to the aggregating effects of arachidonic acid, and increased synthesis of immunoreactive prostaglandin E-like material. More recent studies have shown that platelets obtained from diabetic subjects are less sensitive to the antiaggregatory effects of imidazole, a thromboxane synthetase inhibitor. These observations suggest that increased synthesis of the labile aggregating substance thromboxane A2 also occurs in platelets obtained from diabetics. Collectively, these platelet and plasma abnormalities may contribute to accelerated vascular disease of diabetes. Prospective studies using antiplatelet agents are presently underway or in the planning stages in diabetics to explore their potential beneficial effects.
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PMID:Platelet adhesion and aggregation in diabetes mellitus. 12 93

1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA.
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PMID:Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A. 19 89

In animals the pyruvate dehydrogenase reaction is mainly responsible for the irreversible loss of glucose carbon by oxidation. Regulation of this reaction is shown to be a major determinant of glucose conservation in starvation and diabetes. Estimates of conservation in man in starvation and diabetes are reviewed. The pyruvate dehydrogenase complex is inhibited by products of its reactions; it is also regulated by a phosphorylation-dephosphorylation cycle catalysed by a kinase intrinsic to the complex and by a more loosely associated phosphatase. Inactivation is largely accomplished by phosphorylation of the tetrameric decarboxylase component (alpha2beta2) to alpha2Pbeta2. Complete phosphorylation produces the (alpha2P3)beta2 form. Both forms are completely reactivated by phosphatase action but the initial rate of reactivation of a complex containing alpha2Pbeta2 is approximately three times that of (alpha2P3)beta2. The proportion of active (dephosphorylated) complex is decreased in rat tissues by starvation and diabetes and in perfused rat heart by oxidation of fatty acids and ketone bodies. In adipose tissue in vitro, insulin increases the proportion of active complex and lipolytic hormones may decrease this proportion. It is suggested that rates of oxidation of lipid fuels may be a major determinant of the activity of pyruvate dehydrogenase in tissues in relation to the actions of insulin and lipolytic hormones and the effects of diabetes and starvation. Phosphorylation and inactivation of the complex are enhanced by high mitochondrial ratios of [acetyl-CoA]/[CoA], [ATP]/[ADP], [NADH]/[NAD+] and low concentrations of pyruvate, Mg2+ and Ca2+, and vice versa.
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PMID:Regulation of pyruvate oxidation and the conservation of glucose. 37 69

The levels of ATP, ADP, AMP, inorganic phosphate and 2,3-DPG have been determined in blood and liver of normal and streptozotocin-diabetic rats maintained for up to 11 months on a diet in which the sole carbohydrate source was either starch or sucrose. The feeding of sucrose to normal rats did not significantly alter the adenine nucleotide or phosphate content of the liver and blood. The diabetic state caused a reduction in the ATP, and an increase in AMP and phosphate content of the liver. The feeding of sucrose to the diabetic animals increased the blood phosphate level. The erythrocyte 2,3-DPG content was unaffected by the alterations of ATP and phosphate levels or by the diabetes.
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PMID:The effects of dietary sucrose and streptozotocin-diabetes on blood and liver constituents. 44 Jun 35

ADP-induced platelet aggregation was investigated in patients with diabetes mellitus at various stages of the development of retinopathy. Two parameters were used to evaluate the aggregation activity of platelets: the degree of aggregation and the dysaggregation percentage. There was revealed a direct correlation between the platelet hyperaggregation and the degree of diabetic retinopathy. A sharp elevation of the degree of aggregation and low dysaggregation percentage (up to its complete absence) were noted in patients with proliferating retinopathy; this could be supposed to be due to the supervention of the activating action of the altered vascular wall on the platelet aggregation. No reduction of platelet hyperaggregation under the effect of a brief treatment with such drugs as prodectin and dicion was revealed.
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PMID:[Platelet aggregation in diabetes mellitus at various stages of development of retinopathy]. 47 73

Ischemic optic neuropathy and retinal arterial occlusion are 2 forms of arterial occlusive disease affecting the eye. Reports in the literature suggest platelet hyperactivity in acute arterial occlusive diseases affecting other organ systems. Therefore, 14 patients with ischemic optic neuropathy and 17 patients with central or branch retinal artery occlusion were studied to determine whether platelets have a role in the pathogenesis of these vascular occlusive disorders. The results of the following investigations were no different in these patients compared with those in 18 control patients with non-vascular eye diseases: prothrombin times, partial thromboplastin times, plasma fibrinogen, factor V, factor VIII, platelet counts and threshold concentrations of ADP, epinephrine and collagen resulting in secondary platelet aggregation and serotonin release. In contrast, platelet coagulant activities concerned with the early stages of intrinsic coagulation were significantly increased in patients with retinal artery occlusion without hypertension or type IV hyperlipoproteinemia, but generally normal in patients with ischemic optic neuropathy and in patients with retinal artery occlusion associated with hypertension, type IV hyperlipoproteinemia, diabetes mellitus and generalized atherosclerosis. These results are consistent with a platelet contribution to retinal arterial occlusive disease in patients without other known contributing factors such as hypertension, serum lipid abnormalities, diabetes mellitus and generalized atherosclerosis and may have implications regarding prophylaxis.
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PMID:Platelet coagulant activities in arterial occlusive disease of the eye. 50 1

Platelet functions studied in 163 unselected diabetics compared with 163 controls had the following characteristics: hyperagregation induced by ADP (1.2 muM and 0.6 muM), delayed platelet disagregation (ADP: 0.6 muM), normal agregation in the presence of collagen and thrombin. Platelet hyperagregation induced by ADP was marked in both sexes in cases of retinopathy and in women after the age of 50. By contrast, no correlation was demonstrated between the degree of hyperagregation and age, weight, the duration of diabetes, blood glucose control, lipid profile, vascular complications other than retinopathy and the nature of treatment.
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PMID:[Platelet functions in diabetes with angiopathy (author's transl)]. 53 70

During the first two thirds of gestation, the concentrations of UDPG, ATP, ADP, and Mg++ in human fetal liver remain constant, whereas the concentration of Pi decreases twofold and the G-6-P and AMP concentrations increase. Incubation of human fetal liver explants with glucagon or insulin did not alter the concentrations of any of these intermediates. ATP, ADP, and Pi are inhibitors of human fetal liver glycogen synthase D-form activity, while G-6-P and AMP and Mg++ are stimulators. Ca++ at concentrations of less than 0.1 mM was found to stimulate glycogen synthase D activity. This effect of Ca++ was also observed in "physiologic" mixtures containing UDPG, G-6-P, ATP, ADP, AMP, Pi, and Mg++ at concentrations found either in liver in utero or in explants. 45Ca++ efflux from perifused (rat) fetal liver explants was stimulated by glucagon. These data provide a picture of the metabolite regulation of human fetal liver glycogen synthase activity in which the D-form may largely control glycogen synthesis in utero and hormonal effects on glycogen synthase may be induced by effects of Ca++ on the D-form.
Diabetes 1975 Dec
PMID:Hormonal regulation of glycogen metabolism in human fetal liver. II. Regulation of glycogen synthase activity. 81 98

An increased sensitivity of platelets to aggregation from ADP and epinephrine is described in diabetics with or without vascular disease. This sensitivity correlates with elevated levels on von Willebrand factor (vWF), which, in turn appears to be influenced by growth hormone. VWF activity correlates with previously described "plasma factor" activity. Platelets from diabetic subjects are more sensitive than platelets from normal subjects to arachidonic acid-induced aggregation. This sensitivity is abolished by aspirin, which is a prostaglandin synthetase (cyclo-oxygenase) inhibitor. Platelets from diabetc subjects synthesize increased amounts of PGE2-like material (iPGE) in response to ADP, epinephrine, collagen, and arachidonic acid. The latter finding suggests that a fundamental mechanism for increased platelet aggregation in diabetes is increased prostaglandin synthetase activity. Therapeutic endeavors that would lower growth hormone levels, vWF activity, and/or prostaglandin synthetase activity may be of benefit in the prophylaxis of diabetic vascular disease. Prospective studies are needed to explore these hypothesis, as are more studies on the precise mechanisms and platelet aggregation in diabetes mellitus.
Diabetes 1976
PMID:Altered platelet function in diabetes mellitus. 82 64


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