Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disease states such as diabetes mellitus are known to impair hippocampal glucoregulatory activities, which may contribute to cognitive deficits observed in diabetic subjects. Stress or exposure to stress levels of glucocorticoids (GCs) are also intimately involved in hippocampal glucoregulatory activities and the actions of GCs are often most evident in hyperglycemic states. Glucose transporter (GLUT) expression, activity and translocation represent components of the glucoregulatory activities of the hippocampus that may be disrupted by diabetes and stress. Accordingly, the current study examined the effects of stress, streptozotocin (STZ)-induced diabetes and the combined actions of stress and hyperglycemia upon GLUT8 mRNA expression, protein levels and intracellular trafficking in the rat hippocampus. Short-term stress in euglycemic rats had no effect upon GLUT8 mRNA, while restraint stress normalized diabetes mediated increases in GLUT8 mRNA expression in STZ treated rats. Radioimmunocytochemical analysis revealed that total GLUT8 protein levels were not altered by diabetes, short-term stress or the combined actions of hyperglycemia and stress. However, subcellular compartmentalization of GLUT8 was modulated by stress in that hippocampal GLUT8 protein levels were increased in high-density microsomal (HDM) fractions isolated from rats subjected to stress. In contrast, STZ-diabetes decreased GLUT8 protein levels in the HDM fraction, an effect that was potentiated by stress. Collectively, these results demonstrate that the actions of GCs may be dramatically different in euglycemic and hyperglycemic/insulinopenic states, suggesting that stress may increase hippocampal neuronal responsiveness under normal physiological conditions while increasing hippocampal neuronal vulnerability in pathophysiological settings such as in type 1 diabetes.
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PMID:Biphasic effects of stress upon GLUT8 glucose transporter expression and trafficking in the diabetic rat hippocampus. 1504 21

As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.
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PMID:Screening for associated autoimmunity in type 1 diabetes mellitus with respect to diabetes control. 1571 40

Examination of 91 patients with diabetic retinopathy in the presence of type I diabetes mellitus (DM-1) showed that 56% of the patients had a great variety of organ-specific and organ-nonspecific autoantibodies (AABs), including those to the microsomal and cytoplasmic fractions of endocrine glands, such as pancreas, thyroid, and pituitary. AABs were most common to the pituitary (23.2%), total myelin protein (18.7%), and denatured DNA (17.6%). There were correlations between AAB and the duration of DM-1 more than 20 years (78.3%; p < 0.05), between the total myelin protein AAB and encephalopathy (31.3%; p < 0.05), between the denatured DNA AAB and the increased retinal vascular permeability (29.3%; p < 0.05), which suggests their implication in vascular wall disintegration. No correlations could be found between AAB to the pituitary, pancreas, and thyroid and obvious pathology of the glands. Combined therapy with the immunomodulators thymactid and lycopide yielded a total beneficial effect (AAB disappearance, decreased titers, and no changes) in 88.3% of case while beneficial effect of insulin therapy was obtained in 53.9% of cases, which suggests that it is expedient to include of currently available immunomodulators into traditional insulin therapy.
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PMID:[Systemic autoantibodies and their correction in patients with diabetic retinopathy in type 1 diabetes mellitus]. 1721 99

We report a patient with combined polycystic ovary syndrome (PCOS) and autoimmune polyglandular syndrome (APS) type 2. A 26-year-old female presented with polyuria, polydipsia and acute weight loss. She was diagnosed with: (1) type 1 diabetes, with hyperglycemia, impaired insulin secretion, and positive autoantibodies for GAD-65 and IA-2; (2) autoimmune thyroiditis, with hypothyroidism, positive anti-microsomal and antithyroglobulin antibodies; and (3) PCOS, with hyperandrogenic signs that had developed 5 years earlier, amenorrhea for the previous 6 months, and characteristic multiple microcystic appearance of both ovaries on ultrasonography. She is being treated with multiple subcutaneous insulin injections, thyroxine replacement, and cyclic medroxyprogesterone for the aforementioned diseases, respectively. Although several investigations have reported a relationship between PCOS and the individual components of APS, this is the first report of both syndromes occurring simultaneously. Potential mechanisms for their interrelation and the possibility that PCOS is an autoimmune disease are discussed.
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PMID:A patient with combined polycystic ovary syndrome and autoimmune polyglandular syndrome type 2. 1755 82

To elucidate the pathophysiological significance of adenosine 3'-monophosphate (3'-AMP) forming enzyme in mice, the effect of streptozotocin (STZ) on the enzyme activities and adenine nucleotide levels in the ICR mice (4-week-old) liver was examined. After 2 weeks, treatment with a single dosage of STZ (100, 150 or 200 mg/kg i.p.) induced a dose-dependent hyperglycemia and hypoinsulinemia but had no effect on serum alanine aminotransferase activity, indicating that STZ generated type 1 diabetes without hepatitis. In the diabetic liver, the activities of superoxide dismutase (SOD), catalase and ATP levels decreased, and the microsomal CYP2E1 activity increased. Changes of these biological activities might disrupt the cellular homeostatic balance of reactive oxygen species (ROS) production. The activities of 3'-AMP forming enzyme, one of the ribonucleases, in hepatic homogenates were not altered. However, in the STZ 200 mg/kg group, the cytosolic forming enzyme activities were enhanced, and inversely, the mitochondrial activity was reduced significantly, indicating that the decrease in the mitochondrial activity may be accelerated by development of diabetes due to the decrease in the antioxidant defense system and/or increase in ROS production. With the decrease in the 3'-AMP forming enzyme activity, the levels of 3'-AMP, a P-site inhibitor of adenylate cyclase, in mitochondrial were significantly reduced. These results obtained suggested that change in the mitochondrial 3'-AMP forming enzyme activity might reflect the pathophysiological change of mitochondrial function with the development of diabetes. Our results also suggested that change in cytosolic enzyme activity might serve as a new biomarker of oxidative stress because significant negative correlation between the activities of cytosolic 3'-AMP forming enzyme and SOD was found in the early stage of diabetes.
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PMID:Hepatic changes in adenine nucleotide levels and adenosine 3'-monophosphate forming enzyme in streptozotocin-induced diabetic mice. 1854 12

The prevalence of diabetes and other autoantibodies in patients with recently diagnosed youth onset diabetes was evaluated. Fifty-seven patients (95% black, age 19 +/- 5 years, 36% male, diabetes duration 2.6 +/- 2.2 years) were clinically diagnosed as having type 1 (n = 35), type 2 (n = 13) and lipoatrophic diabetes (n = 3) while 6 remained untyped. GAD65 was the most common diabetes-associated autoantibody in patients with type 1A diabetes (12/17; 71%). The prevalence of any diabetes-associated autoantibodies decreased with diabetes duration (OR[95%CI]/yr after diagnosis 0.50[0.31,0.82]) and was not associated with age of onset, duration or gender. Rheumatoid factor (13/57; 23%), smooth muscle (6/57; 11%), gastric-parietal cell (5/57; 9%) and thyroid microsomal antibodies (5/57; 9%) were the most frequent non-diabetes associated autoantibodies and were more common in patients with type 1A diabetes. Only one patient had clinical autoimmune disease (hypothyroidism). Type 1A diabetes may constitute up to half the cases of newly diagnosed type 1 diabetes in Jamaican youth and is associated with a higher prevalence of other organ-specific autoantibodies.
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PMID:Autoantibodies in Caribbean youth with diabetes mellitus. 1902 62

There are no studies that compare the prevalence of organ-specific autoantibodies (OSAs) between adult (>or= 16 years) and childhood-onset type 1 diabetes (T1D). We evaluated the prevalence of the following OSAs: thyroid peroxidase, thyroid receptor, parietal cell, intrinsic factor, tissue transglutaminase, adrenal cortex, mitochondrial, smooth muscle, liver kidney microsomal, and ovarian autoantibodies. Three hundred twenty-seven (327) adults were screened for one or more of these OSAs. The prevalence of all the OSAs studied was similar in both groups. The most prevalent OSA observed was tissue transglutaminase (childhood-onset disease = 14.3%; adult-onset disease = 13.6%). This study did not demonstrate a distinct difference in the prevalence of OSAs between adult- and childhood-onset T1D patients.
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PMID:Prevalence of organ-specific autoantibodies in childhood- and adult-onset type 1 diabetes. 1912 Mar 8

In diabetic patients, an early index of peripheral neuropathy is the slowing of conduction velocity in large myelinated neurons and a lack of understanding of the basic pathogenic mechanisms hindered therapeutics development. Racemic (R/S)-guaifenesin (1) was identified as a potent enhancer of neurite outgrowth using an in vitro screen. Its R-enantiomer (R)-1 carried the most biological activity, whereas the S-enantiomer (S)-1 was inactive. Focused structural variations to (R/S)-1 was conducted to identify potentially essential groups for the neurite outgrowth activity. In vivo therapeutic studies indicated that both (R/S)-1 and (R)-1 partially prevented motor nerve conduction velocity slowing in a mouse model of type 1 diabetes. In vitro microsomal assays suggested that compounds (R)-1 and (S)-1 are not metabolized rapidly, and PAMPA assay indicated moderate permeability through the membrane. Findings revealed here could lead to the development of novel drugs for diabetic neuropathy.
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PMID:Guaifenesin derivatives promote neurite outgrowth and protect diabetic mice from neuropathy. 2375 73


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