Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A decrease in the vitamin E content of human diabetic platelets is closely associated with the accelerated platelet aggregation and platelet prostaglandin metabolism seen in patients with diabetes mellitus. We investigated the effect of vitamin E supplementation on these abnormalities of physiological function and prostaglandin metabolism in 14 non-insulin dependent diabetics with proliferative retinopathy. ADP-induced platelet aggregation was inhibited in vitro by the addition of vitamin E in a dose-dependent manner. However, in lower concentrations considered to be physiological doses in vivo, significantly greater inhibition was observed in diabetic platelets than in the control platelets. Next, alpha-tocopheryl nicotinate was administered to diabetics at a daily dose of 600 mg. The platelet vitamin E content was restored to control levels in 13 of the 14 patients after 2-4 weeks of daily administration. The ADP-induced platelet aggregation rate, platelet thromboxane B2 (TXB2, a stable metabolite of TXA2, a vasoconstrictor production, and plasma TXB2 level were low in all 14 diabetics. In contrast, plasma 6-keto-PGF 1 alpha (a stable metabolite of PGI2, a vasodilator) was significantly increased and therefore the 6-keto-PGF 1 alpha/TXB2 ratio in plasma was restored to within normal limits. These results indicate that vitamin E may improve platelet function and prostaglandin metabolism in diabetes mellitus and may be able to provide further beneficial effects in relation to the development of diabetic vascular complications.
Diabetes Res 1990 May
PMID:Effects of vitamin E administration on platelet function in diabetes mellitus. 213 64

A 2-year randomized placebo-controlled double-blind trial of 250 mg day-1 of the aldose reductase inhibitor Sorbinil in severe symptomatic chronic peripheral neuropathy was performed in 21 diabetic patients. Due to adverse reactions 8 patients completed the trial on Sorbinil and 6 patients on placebo. Despite differences in baseline neurophysiological parameters, duration of diabetes, and presence of retinopathy between the placebo and treatment groups, there were no initial differences in in vitro platelet aggregation, albumin excretion rate (AER) or muscle capillary basement membrane thickness. After 2 years the median deterioration in AER in the placebo group was 18.4 micrograms min-1 (range 2.6-64.8 micrograms min-1). This deterioration was significant (p less than 0.03). The change in AER in the Sorbinil group was +1.25 (-10.7 to +20.4) micrograms min-1, an insignificant change. In vitro platelet responsiveness to collagen and adenosine diphosphate (ADP) increased in the placebo group (median change max% collagen + 8 (+2 to +30)%; ADP +4.5 (0 to +20)% compared with a fall in the Sorbinil treated patients (median change; collagen -17.5 (-2 to -40)%, p less than 0.05; ADP, -4 (0 to -25)%, p less than 0.05). Muscle capillary basement membrane thickness was measured in only 3 patients in each group and did not alter significantly during the trial. All 12 neurophysiological measurements showed no significant changes between the treatment and placebo groups. The data suggest that aldose reductase inhibition has effects on platelet reactivity and microalbuminuria.
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PMID:Prolonged aldose reductase inhibition in chronic peripheral diabetic neuropathy: effects on microangiopathy. 213 66

Patients with diabetes mellitus are prone to develop vascular complications. Because omega-3 polyunsaturated fatty acid (omega 3FA) intake has a potential protective effect on cardiovascular disease, we studied the influence of omega 3FA supplementation (5.4 g eicosapentaenoic acid and 2.3 g docosahexaenoic acid daily) for 4 wk in 13 well-controlled type I (insulin-dependent) diabetic subjects on a vascular risk profile. Each subject served as his/her own control in a pre- and post-omega 3FA-intake phase. In plasma and platelets, phospholipids eicosapentaenoic acid and docosahexaenoic acid increased at the expense of arachidonic acid and linoleic acid. There was no significant change in blood pressure and glycosylated proteins. Only small changes were noted in blood glucose levels and insulin dose. Side effects were not noted. Triglycerides decreased significantly in the first 14 days, and total cholesterol increased slightly, probably because of an elevation of high-density lipoprotein cholesterol, although low-density lipoprotein cholesterol remained unchanged. Platelet aggregation induced by low doses of ADP and collagen, which was higher in diabetic than nondiabetic subjects, decreased during omega 3FA intake to levels of healthy control subjects. Thromboxane production after ADP- and collagen-induced platelet aggregation decreased significantly. Thromboxane liberation during clotting of whole blood and urinary excretion of thromboxane were markedly lowered during omega 3FA supplementation. The results show that even short-term intake of omega 3FAs leads to beneficial changes of vascular risk factors without significant changes in glucose homeostasis.
Diabetes 1990 Mar
PMID:Pilot study on omega-3 fatty acids in type I diabetes mellitus. 213 3

Normal mouse islet cells express low levels of MHC class I molecules and undetectable or extremely low levels of MHC class II molecules. Class I expression was dose-dependently augmented by incubation with interferon-gamma (IFN-gamma) or tumor necrosis factor (TNF). Although neither IFN-gamma nor TNF alone induce class II molecules on islet cells, synergistic interaction of IFN-gamma (200 U/ml) and TNF (200 U/ml) may induce class II expression on approximately 50% of islet cells. Niacinamide and 3-aminobenzamide, both inhibitors of ADP ribosylation and scavengers of free radicals, attenuated the class II expression induced by IFN-gamma and TNF. Twenty millimolar niacinamide and 10 mM 3-aminobenzamide reduced the rates of class II antigen-positive cells to mean +/- SD 3.6 +/- 0.3 and 6.1 +/- 1.9%, respectively. The agents did not affect the cytokine-induced augmentation of class I antigens. The inhibition of class II molecule expression may at least partly account for the preventive effect of niacinamide on autoimmune-associated beta-cell damage in NOD mice.
Diabetes 1990 Sep
PMID:Inhibition of cytokine-induced MHC class II but not class I molecule expression on mouse islet cells by niacinamide and 3-aminobenzamide. 214 88


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