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)

A recombinant-antigen enzyme immunoassay (EIA), BioSCREEN anti-Treponema pallidum, was compared favorably with the T. pallidum hemagglutination test, in the detection of specific antibodies in different groups of sera from patients with primary (n = 38), secondary (n = 10), early latent (n = 28) and congenital syphilis (n = 2), patients with leptospirosis ( n= 8), infectious mononucleosis (n = 7), hepatitis (n = 9), diabetes mellitus (n = 11), rheumatoid arthritis (n = 13), leprosy (n = 11), tuberculosis (n = 9), HIV/Aids ( n= 12), systemic lupus erythematosus (n = 4), rheumatic fever (n = 3), old-persons (n = 9), pregnant women (n = 29) and blood donors (n = 164). The coincidence between them was 95.1%. The sensitivity and specificity of the EIA were 93.3% and 95.5%, respectively. Fifteen serum specimens belonging to old-persons, pregnant women, blood donors, and patients with human leptospirosis, hepatitis, diabetes mellitus, tuberculosis and rheumatic fever gave false-positive results by Venereal Disease Research Laboratory and/or Rapid Plasma Reagin. The EIA can be used as alternative method for the serological confirmation of syphilis.
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PMID:Comparison of a recombinant-antigen enzyme immunoassay with Treponema pallidum hemagglutination test for serological confirmation of syphilis. 1204 63

Diabetes is associated with extensive microvascular pathology and decreased expression of the glucose transporter (GLUT-1) in retina, but not brain. To explore the basis of these differences, the authors simultaneously measured glucose influx (micromol x g(-1) x min(-1)) and blood flow (mL x g(-1) x min(-1)) in retina and brain cortex of nondiabetic control rats (normoglycemic and acute-hyperglycemic) and in rats with streptozotocin-induced diabetes (with or without aminoguanidine (AMG) treatment) using a single-pass, dual-label indicator method. In addition, tissue glucose and adenosine triphosphate (nmol/mg dry weight) levels were measured. Glucose influx in retina exceeded that of cortex by about threefold for both the nondiabetic and diabetic groups. In contrast, blood flow in retina was significantly lower than in cortex by about threefold for each group. Retinal and cortical glucose influx in the diabetic rats was lower than in the nondiabetic acute-hyperglycemic group, but not in the normoglycemic group. Blood flow in these tissues remained relatively unchanged with glycemic conditions. The glucose levels in the diabetic retina (aminoguanidine untreated and aminoguanidine treated) were fourfold to sixfold greater than the nondiabetic retina. The cortical glucose levels remained unchanged in all groups. These data suggest that the accumulation of glucose in the diabetic retina cannot be explained by increased endothelial-glucose uptake or increased vascular membrane permeability.
J Cereb Blood Flow Metab 2004 Apr
PMID:Comparison of glucose influx and blood flow in retina and brain of diabetic rats. 1508 14

Intensive insulin therapy in patients with type 1 diabetes mellitus reduces long-term complications; however, intensive therapy is also associated with a three-fold increase in hypoglycemic episodes. The present study in conscious rats characterizes the physiologic and neuropathologic consequences of a single episode of moderate hypoglycemia. In this model, intravenous insulin is used to reduce plasma glucose to 30 to 35 mg/dL for 75 mins. This single hypoglycemic insult acutely induces hypoglycemia-associated autonomic failure (HAAF), with epinephrine responses to hypoglycemia reduced more than 36% from control. Neuropathology after this insult includes the appearance of dying cells, assessed with the marker Fluoro-jade B (FJ). After hypoglycemic insult, FJ+ cells were consistently seen in subdivisions of the medial prefrontal cortex, the orbital cortex, and the piriform cortex. There was a significant correlation between depth of hypoglycemia and number of FJ+ cells, suggesting that there is a critical threshold below which vulnerable cells begin to die. These data suggest that there is a population of cells that are vulnerable to moderate levels of hypoglycemia commonly experienced by patients with insulin-treated diabetes. These cells, which may be neurons, are primarily found in cortical regions implicated in visceral perception and autonomic control, raising the possibility that their loss contributes to clinically reported deficits in autonomic and perceptual responses to hypoglycemia.
J Cereb Blood Flow Metab 2005 Dec
PMID:Cortical Fluoro-Jade staining and blunted adrenomedullary response to hypoglycemia after noncoma hypoglycemia in rats. 1590 94

Although thiazolidinediones suppress hyperglycemia in diabetic (NON x NZO)F1 males, these mice exhibit unusual sensitivity to drug-induced exacerbation of an underlying hepatosteatosis only rarely experienced in human patients. To establish the pharmacogenetic basis for this sensitivity, a panel of recombinant congenic strains (RCSs) with varying degrees of obesity and diabetes was generated by fixing selected NZO HlLt alleles on the diabetes- and hepatosteatosis-resistant NON/Lt background. Four new strains in this panel were exposed to chronic rosiglitazone treatment. Only one, NONcNZO8 (designated RCS8), exhibited an F1-like hepatosteatotic response. In both the F1 and RCS8 males, this adverse effect correlated with rosiglitazone suppression of already impaired hepatic phosphatidylcholine biosynthetic enzymes in both arms of the biosynthetic pathway, the phosphatidylethanolamine methyl- transferase pathway, and the CDP-choline pathway, including choline kinase and CTP-cholinephosphate cytidylyltransferase. This adverse response was not reproduced by CL316,243, a beta3-adrenergic receptor agonist with potent antihyperlipemic effects. Genome comparison showed that RCS8 differed from the other strains in carrying NZO-derived genome on virtually all of chromosome 16 and in smaller segments on chromosomes 6, 14, and 17. Thus, these RCSs present a panel of new mouse models exhibiting differential levels of obesity and diabetes as well as different drug responses. This panel can be used to screen for treatments for type 2 diabetes and its complications.
Diabetes 2005 Jun
PMID:Pharmacogenetic analysis of rosiglitazone-induced hepatosteatosis in new mouse models of type 2 diabetes. 1591 9

Although the Virchow's triad on thrombosis includes reduced blood flow as a factor, there has been relatively little data on the importance of total cerebral blood flow on the risk of subsequent stroke. In the current study, we investigate whether total cerebral blood flow helps predict stroke recurrence. Extracranial arterial blood flow volume estimated by color velocity imaging quantification ultrasound (CVIQ) is an index of cerebral blood flow measurement. We performed a cohort study of 210 consecutive acute stroke patients. Patients were studied with transcranial Doppler and duplex ultrasound for intra- and extracranial large artery disease within 3 days of symptom onset. The association between the risk of recurrent stroke and CVIQ was analyzed with Cox proportional hazards model. Thirty-nine patients (17.7%) developed an ischemic stroke during a mean follow-up of 47.5 months. The mean extracranial blood flow volume was significantly lower for patients who had a recurrent stroke than those without (594.4+/-130.3 versus 683.8+/-176.9 mL/min; P=0.003). In a Cox proportional hazards model adjusting for potential confounding variables, extracranial blood flow volume (hazard ratio (HR) for lowest tertile, 4.1; 95% confidence interval (CI), 1.5 to 11.0) along with male sex (HR, 2.5; 95% CI, 1.3 to 5.1), diabetes (HR, 2.5; 95% CI, 1.2 to 5.0) and large artery stenosis (HR, 2.2; 95% CI, 1.1 to 4.4) were independent predictors for stroke recurrence. Our data indicated that patient with low amount of blood flow to the brain is at risk of recurrent stroke.
J Cereb Blood Flow Metab 2007 Apr
PMID:Total cerebral blood flow estimated by color velocity imaging quantification ultrasound: a predictor for recurrent stroke? 1698 7

Phosphatidylcholine is an essential phospholipid that is synthesized by 2 different pathways, the CDP-choline pathway and the methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase (PEMT). Recent studies have suggested that PEMT is an important consumer of methyl groups from S-adenosylmethionine (SAM) and is a major determinant of homocysteine pools. Diabetes and all-trans-retinoic acid (ATRA) have been shown to alter the activities of several enzymes involved in methyl group metabolism. Thus, we investigated how diabetes and ATRA, individually and together, affect SAM-dependent phospholipid methylation. Rats received a single injection of streptozotocin (60 mg/kg body wt) or vehicle followed by administration of ATRA (30 mumol/kg body wt) or vehicle for 5 d. The hepatic activity of PEMT increased 50% in both diabetic rat groups, whereas administration of ATRA was without effect. In diabetic rats, plasma total homocysteine decreased 30-35% in all treatment groups as compared with the control group. Thus, alterations in the activity of PEMT were not directly correlated to changes in homocysteine concentrations. Moreover, treatment of diabetic rats with insulin prevented the increase in PEMT activity and abundance. Because these observations support an increased need for SAM-dependent phosphatidylcholine synthesis, this may also indicate an increased choline requirement in diabetes.
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PMID:Hepatic phosphatidylethanolamine N-methyltransferase expression is increased in diabetic rats. 1711 11

Cerebral vascular dysfunction and associated diseases often occur in type-1 diabetes, but the underlying mechanisms are largely unknown. In this study, we sought to determine whether big-conductance, Ca(2+)-activated K(+) (BK) channels were impaired in vascular (cerebral artery) smooth muscle cells (CASMCs) from streptozotocin-induced type-1 diabetic mice using patch clamp, molecular biologic, and genetic approaches. Our data indicate that the frequency and amplitude of spontaneous transient outward currents (STOCs) are significantly decreased, whereas the activity of spontaneous Ca(2+) sparks is increased, in diabetic CASMCs. The sensitivity of BK channels to voltage, Ca(2+), and the specific inhibitor iberiotoxin are all reduced in diabetic myocytes. Diabetic mice show increased myogenic tone and decreased contraction in response to iberiotoxin in cerebral arteries and elevated blood pressure. The expression of the BK channel beta1, but not alpha-subunit protein, is markedly decreased in diabetic cerebral arteries. Diabetic impairment of BK channel activity is lost in CASMCs from BK channel beta1-subunit gene deletion mice. In conclusion, the BK channel beta1-subunit is impaired in type-1 diabetic vascular SMCs, resulting in increased vasoconstriction and elevated blood pressure, thereby contributing to vascular diseases in type-1 diabetes.
J Cereb Blood Flow Metab 2008 Feb
PMID:Functional and molecular evidence for impairment of calcium-activated potassium channels in type-1 diabetic cerebral artery smooth muscle cells. 1768 20

Neuropathy accompanied by abnormal sensory perception is the most common complication in insulin-dependent and -independent diabetes mellitus. Since there are very few effective therapeutic regimens for sensory abnormalities in diabetes, we examined the effect of cytidine 5'-diphosphocholine (CDP)-choline on the thermal nociceptive threshold in streptozotocin-induced diabetic mice using the tail-flick test. Diabetic mice showed a shorter tail-flick latency at 1-4 weeks after streptozotocin treatment and a longer tail-flick latency after 8-12 weeks. This hyper- and hypoalgesia in diabetic mice was almost completely inhibited by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning on the day of streptozotocin treatment. Daily treatment with CDP-choline beginning 5 weeks after streptozotocin treatment attenuated the development of hypoalgesia. Diabetic mice showed a significant increase in Na(+)-K(+)-ATPase activity at 3 weeks after streptozotocin treatment, whereas Na(+)-K(+)-ATPase activity was decreased at 12 weeks after treatment. These alterations were normalized by daily treatment with CDP-choline (100 mg/kg/day, p.o.) beginning the day of streptozotocin treatment. These results provide evidence to support the therapeutic potency of CDP-choline on the development of thermal hyper- and hypoalgesia and the progression of thermal hypoalgesia in diabetic mice. Moreover, these effects of CDP-choline may result from the normalization of Na(+)-K(+)-ATPase activity.
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PMID:Effects of cytidine 5'-diphosphocholine (CDP-choline) on the thermal nociceptive threshold in streptozotocin-induced diabetic mice. 1883 78

Diabetic retinopathy (DR) is the leading cause of vision loss as a major complication of diabetes mellitus. The blood-retinal barrier (BRB) breakdown is a critical early event in the pathogenesis of DR. It has been known that the rennin-angiotensin system (RAS) is important in the progression of the DR via angiotensin II (Ang II), the effector of RAS. In this study, we showed that blockade of Ang II attenuates vascular endothelial growth factor (VEGF)-mediated BRB breakdown in DR. In streptozotocin-induced diabetes, retinal vascular permeability increased with upregulation of VEGF, where Ang II and its receptors were upregulated. Ang II induced VEGF expression in retinal endothelial cells accompanied by loss of tight junction proteins. However, the blockade of Ang II by perindopril, an angiotensin converting enzyme (ACE) inhibitor, inhibited upregulation of VEGF, and prevented the loss of tight junction proteins. Moreover, inhibition of Ang II by perindopril attenuated increased vascular permeability of diabetic retina accompanied by recovery of tight junction proteins in retinal vessels. Therefore, we suggest that the RAS involves in increased vascular permeability during early stage of DR, which is mediated by VEGF. Furthermore, the ACE inhibitor may have a therapeutic potential in the treatment of diabetic BRB breakdown.
J Cereb Blood Flow Metab 2009 Mar
PMID:Blockade of angiotensin II attenuates VEGF-mediated blood-retinal barrier breakdown in diabetic retinopathy. 1910 35

The risk of severe hypoglycemia in patients with type I diabetes and high basal activity in the renin-angiotensin system (RAS) is significantly higher than in patients with low basal RAS activity. In healthy men, we tested the hypothesis that differences in spontaneous RAS activity are associated with differences in cerebral activity responses during mild hypoglycemia. A total of 10 healthy men with high and 10 with low spontaneous RAS activity were selected. An H(2)(15)O-PET (H(2)(15)O-positron emission tomography) study was conducted with a series of six scans, i.e., two during normoglycemia, two during hypoglycemia, and two after hypoglycemia. The mean plasma glucose concentration was similar in both the groups (i.e., 2.1 mmol/L (s.d.: 0.4) in the low RAS group and 2.2 mmol/L (s.d.: 0.4) in the high RAS group (P=0.47)). The high RAS group has lower cerebral activity in the frontal area and a higher cerebral activity in the entorhinal area that expanded to include the parahippocampal gyrus after hypoglycemia. Our findings suggest that the high RAS group to a lesser extent than the low RAS group activates areas involving executive function that may explain the correlation between high basal RAS activity and risk of severe hypoglycemia in type I diabetes.
J Cereb Blood Flow Metab 2009 Nov
PMID:Association between regional cerebral blood flow during hypoglycemia and genetic and phenotypic traits of the renin-angiotensin system. 1958 89


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