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

Platelet count, spontaneous platelet aggregation, ADP- and collagen-induced platelet aggregation platelet adhesion, platelet volume, shape change, beta-thromboglobulin and von-Willebrand-factor have been investigated in 51 insulin dependent diabetic children without clinical signs of diabetic angiopathy. Compared to an age matched healthy control group diabetic children showed a significant enhancement of spontaneous platelet aggregation, elevated plasma levels of von-Willebrand-factor, increased platelet shape change and adhesion. No alterations could be found in ADP--and collagen--induced platelet aggregation and in beta-thromboglobulin levels. Significant correlations could be found between the total glycosylated haemoglobin concentrations (Hb A1) and spontaneous platelet aggregation, as well as between duration of diabetes Hb A1, and platelet volume. In this study we could demonstrate changes in platelet function in diabetic children without clinical signs of diabetic angiopathy. However these changes could be due to metabolic adjustment and may precede diabetic vasculopathy.
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PMID:[Thrombocyte function in children with Type I diabetes mellitus. Cross-sectional study]. 177 Sep 58

The effects of vitamin E and D-myo-inositol 1,2,6-trisphosphate (PP-56) were investigated in long-term studies in streptozocin-induced diabetic rats fed a purified diet with 33% lipids and a polyunsaturated-to -saturated fatty acid ratio of 1. A supplement of vitamin E decreased plasma triglycerides, platelet lipid biosynthesis, some of the delta 6- and delta 5-desaturase abnormalities, and urine ketone bodies but did not affect the response of platelets to aggregation. PP-56 completely normalized the platelet reactivity to ADP and thrombin. This was accompanied by normalization of platelet lipid biosynthesis and diabetes-induced abnormalities in delta 6- and delta 5-desaturases. PP-56 treatment also reduced the mortality rate and to a certain extent urinary ketone bodies. The protective effect of PP-56 on platelet aggregation and mortality rate were dose related. PP-56, a molecule derived from phytic acid, seems to exert potent protective effects on some of the manifestations associated with diabetes in rats.
Diabetes 1991 Feb
PMID:Effects of PP-56 and vitamin E on platelet hyperaggregability, fatty acid abnormalities, and clinical manifestations in streptozocin-induced diabetic rats. 182 73

Euglycemic (approximately 5.5 mM) hyperinsulinemic clamps were performed on normoglycemic insulin-sensitive (NIS) men and men who were normoglycemic but insulin resistant (NIR) and hyperglycemic and insulin resistant (HIR) (i.e., noninsulin-dependent diabetes mellitus). Insulin was infused at successive rates of 40 and 400 mU.m-2.min-1, and biopsies were obtained from the quadriceps femoris muscles before and after insulin and analyzed for regulators of phosphofructokinase, a rate-limiting enzyme for glycolysis. Glucose disposal and whole body carbohydrate oxidation were markedly lower in NIR and HIR vs. NIS (P less than 0.001 for disposal and oxidation). The alpha-D-glucose 1,6-bisphosphate (G-1,6-P2) content increased almost twofold during the 40-mU insulin infusion (P less than 0.001) without any further change during the 400-mU infusion in NIS men. The increase in G-1,6-P2 in NIR and HIR was only approximately 25 and 50% of the increase observed in NIS during the 40- and 400-mU infusions, respectively. The mean content of G-1,6-P2 was strongly related to the mean rate of carbohydrate oxidation (r = 0.99; P less than 0.001). Because during euglycemic hyperinsulinemia approximately 90% of the glucose utilization is accounted for by skeletal muscle (J. Clin. Invest. 76: 149, 1985), it is likely that whole body carbohydrate oxidation is proportional to carbohydrate oxidation and glycolysis in muscle. The different rates of carbohydrate oxidation between NIS and insulin-resistant men could not be associated with differences in fructose 6-phosphate, fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, Pi, free ADP and free AMP (activators of phosphofructokinase), or ATP and citrate (inhibitors of phosphofructokinase).
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PMID:Relationship between carbohydrate oxidation and G-1,6-P2 in human skeletal muscle during euglycemic hyperinsulinemia. 182 56

The goal of this study was to determine the mechanism of impaired responses of cerebral arterioles during diabetes mellitus. To induce diabetes, rats were injected with streptozotocin. Rats were characterized as diabetic by a blood glucose of greater than 300 mg/dl. Diameter of pial arterioles was measured with intravital microscopy in nondiabetic and diabetic rats during superfusion with acetylcholine (ACh), ADP, the thromboxane (Tx) analogue U-46619, and nitroglycerin. ACh increased pial arteriolar diameter in nondiabetic rats and did not alter diameter in diameter in diabetic rats. ADP increased pial arteriolar diameter in nondiabetic rats and produced minimal changes in diameter of arterioles in diabetic rats. Tx analogue U-46619 produced similar constriction of cerebral arterioles in nondiabetic and diabetic rats. In addition, nitroglycerin produced similar dilatation of cerebral arterioles in nondiabetic and diabetic rats, suggesting that impaired dilatation of cerebral arterioles in diabetic rats was not related to nonspecific impairment of vasodilatation. Next, we examined the possibility that impaired responses of cerebral arterioles in diabetic rats in response to ACh and ADP may be related to production of a cyclooxygenase constrictor substance. Indomethacin and the TxA2-prostaglandin (PG) H2 receptor antagonist SQ 29548 restored dilator responses to ACh and ADP in diabetic rats toward that observed in nondiabetic rats. Indomethacin and SQ 29548 did not alter responses in nondiabetic rats. Thus diabetes mellitus impairs endothelium-dependent responses of cerebral arterioles. The mechanism of impaired responses of cerebral arterioles during diabetes mellitus appears to be related to the production of a cyclooxygenase constrictor substance and presumably related to stimulation of the TxA2-PGH2 receptor.
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PMID:Mechanism of impaired responses of cerebral arterioles during diabetes mellitus. 182 54

Glucose is the principal source for energy production in the brain, and undisturbed glucose metabolism is pivotally significant for normal function of this organ. Peripheral glucose metabolism is impaired by streptozotocin (STZ), which induces diabetes mellitus. In this investigation, we have studied the local effects of intracerebroventricular (i.c.v.) STZ on glucose and energy metabolism in cerebral cortex. Three weeks after one single i.c.v. administration of STZ, ATP and phosphocreatine (CrP) concentrations as well as the ATP/ADP ratio and the energy charge potential were decreased, while the concentrations of glucose and ADP were increased, in cerebral cortex. Arterial blood glucose levels were not altered by i.c.v. STZ. It is concluded that brain energy metabolism is locally impaired by i.c.v. STZ. We propose that the disturbance of brain energy metabolism by i.c.v. STZ administration may provide a model for the study of prolonged metabolic neuronal stress.
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PMID:Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. 183 65

Guanine nucleotide-binding proteins (G proteins) are critically important mediators of many signal-transduction systems. Several important sites regulating stimulus-secretion coupling and release of insulin from pancreatic beta-cells are modulated by G proteins. Gs mediates increases in intracellular cAMP associated with hormone-induced stimulation of insulin secretin. Gi mediates decreases in intracellular cAMP caused by inhibitors of insulin secretion, e.g., epinephrine, somatostatin, prostaglandin E2, and galanin. G proteins also regulate ion channels, phospholipases, and distal sites in exocytosis. Cholera and pertussis toxins irreversibly ADP ribosylate G proteins and are important tools that can be used both to manipulate G-protein-dependent modulators of insulin secretion and detect and quantify G proteins by electrophoretic techniques. The stage is set to pursue these initial observations in greater depth and ascertain whether G-protein research will provide important new insights into normal and abnormal regulation of insulin secretion.
Diabetes 1991 Jan
PMID:G proteins and modulation of insulin secretion. 190 7

Adenylate cyclase activity was examined as a measure of inhibitory guanine nucleotide binding protein (Gi) function in liver plasma membranes from rats made chemically diabetic by streptozotocin (STZ) treatment. Clonidine activation of the alpha 2 adrenergic receptor, which activates Gi, inhibited forskolin--stimulated adenylate cyclase activity in control membranes. However, there was no effect on adenylate cyclase activity in membranes from STZ diabetic animals. Also, a polyclonal antipeptide antibody was raised to a highly conserved segment of the Gi alpha 2 subunit. This antibody specifically recognizes a 41 kilodalton protein, is blocked by an excess of peptide, does not recognize the alpha-subunit of transducin, and immunoprecipitates a 41 kilodalton protein which was ADP-ribosylated by pertussis toxin. Immunoblots using this antibody detect no difference between normal and STZ diabetic animals in the level of liver plasma membrane Gi expression. Therefore, STZ-induced diabetes altered the function of Gi but had no effect on Gi expression.
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PMID:The function but not the expression of rat liver inhibitory guanine nucleotide binding protein is altered in streptozotocin-induced diabetes. 190 25

The activity of human platelet guanylate cyclase, and the activation of the enzyme by sodium nitroprusside were decreased in platelets with increased aggregability; these platelets were obtained from diabetes mellitus patients. Anomalies in guanylate cyclase activity and ADP-induced aggregation were more pronounced in platelets from subjects with type II than those with type I diabetes.
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PMID:Guanylate cyclase in human platelets with different aggregability. 197 57

AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).
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PMID:Changes in AMP deaminase activities in the hearts of diabetic rats. 202 37

In vitro platelet aggregation in response to a wide range of final adenosine-5'-diphosphate (ADP) concentrations was assessed in 11 young, diabetic males without detectable vascular complications and in 11 closely-matched controls. First phase aggregation was assessed using a particle collision theory model and the "sigmoid Emax" dose-response equation. Platelets from the diabetics required a significantly lower ADP concentration to attain a sticking probability of 0.2 (EC20; median [95% confidence limits]; 0.38 mumol/l ADP [0.25-0.52]) than those from the controls (0.55 mumol/l [0.28-0.67]; p = 0.016). At higher concentrations (EC50, EC80), there were no significant differences between the two groups (p greater than 0.05). Second phase aggregation, assessed from threshold for initiation of the release reaction, occurred at lower ADP concentrations in the diabetic group (2.0 mumol/l [1.2-4.4] vs 3.2 mumol/l [1.6-7.0]; p = 0.009). Consistent with the multistep nature of ADP-induced aggregation, these results indicate dose-dependent platelet function abnormalities in diabetics without vasculopathy. Enhanced reversible microaggregate formation (associated with platelet shape change) at low ADP concentrations may precede other first phase changes in early diabetes and would explain apparent inconsistencies in the results of previous studies involving similar subject groups.
Diabetes Res 1990 Nov
PMID:Dose-dependent increase in in vitro platelet sensitivity to adenosine-5'-diphosphate in young complication-free diabetic males. 213 1


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