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)

We describe a new method for the detection of different types of pathological autoantibodies against TSH receptor (TSHR) in Graves' patients sera by luminescent immunoprecipitation analysis. For this purpose three different chimeras composed of human TSHR and rat luteotropin/choriogonadotropin receptor (LH-CGR) were constructed, as was described previously (Tahara K, Ishikawa N, Yamamoto K, Hirai A, Ito K, Tamura Y, Yoshida S, Saito Y, Kohn LD. 1997 Thyroid 7:867-877). They were used in the immunoprecipitation reactions: (i) the wild type TSHR (for the detection of total TSHR autoantibodies), (ii) TSHR/LH-CGR chimera wherein TSHR amino acid residues 8-165 (epitopes for thyroid stimulating antibodies) are replaced by comparable LH-CGR residues, (iii) TSHR/LH-CGR chimera wherein TSHR amino acids 261-370 (epitopes for thyroid blocking antibodies) are replaced by comparable LH-CGR residues, and (iv) TSHR/LH-CGR chimera wherein TSHR amino acids 8-165 and 261-370 are replaced by comparable LH-CGR residues (for the detection of neutral TSHR autoantibodies). DNA encoding the N-terminal 725 (of 764) amino acids of wild type TSHR (or TSHR/LH-CGR chimera) was fused to the cDNA for the 550-amino acid firefly luciferase. The hybrid proteins were produced in HeLa cells using recombinant vaccinia viruses. All fusion proteins retained the enzymatic activity of firefly luciferase and TSHR-LUC interacted with TSH with the same affinity as wild type receptor. The luciferase tagged TSHR and TSHR/LH-CGR chimeras were used for the detection of different types of TSHR autoantibodies (i.e. total, neutral, thyroid stimulating and thyroid blocking) in 63 Graves' disease and 62 normal sera by immunoprecipitation analysis. The data demonstrated positive correlation between results of immunoprecipitation assay and results obtained using cAMP bioassay or assay for TSH binding inhibitory immunoglobulins in test sera.
Exp Clin Endocrinol Diabetes 2000
PMID:Detection of functionally different types of pathological autoantibodies against thyrotropin receptor in Graves' patients sera by luminescent immunoprecipitation analysis. 1082 18

Recent studies have shown that related genetic influences on bone mineral density (BMD) and bone turnover are related to allelic variations in the vitamin D receptor (VDR) gene. Osteoporosis as a complication of hyperthyroidism is characterized by increased rates of both bone formation and bone resorption. In addition, VDR gene polymorphism influences susceptibility to some autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM) and multiple sclerosis (MS). In the gene encoding the VDR, we investigated the distribution of a VDR-FokI polymorphism that changes the predicted protein sequence. The subjects were 131 female Japanese patients with Graves' disease and 150 female controls. The distribution of genotype frequencies differs between Graves' disease and controls (chi2 = 5.99, degrees of freedom = 2, p = 0.0386). We found overexpression of F allele (69% vs. 61%, p = 0.0472) and homozygote FF (48% vs. 33%, p = 0.0118) in Graves' disease patients compared with controls. We also correlated a VDR-FokI polymorphism with BMD in the distal radius and biochemical markers of bone turnover in patients with Graves' disease in remission. Although generally no significant association was seen between age-adjusted BMD and genotype, patients in remission for >5 years showed significantly lower age-adjusted BMD in Ff heterozygotes than in ff homozygotes (Z = 1.14 ff vs. Z = -0.43 Ff, p < 0.05). Moreover, serum concentrations of bone alkaline phosphatase were significantly greater in Ff homozygotes than in FF homozygotes (78 +/- 12 vs. 59 +/- 10, p < 0.05). The genotypes did not differ in serum concentrations of osteocalcin, urinary hydroxyproline, or urinary deoxypyridinoline. Our results indicate, for the first time, an association between Graves' disease and a VDR polymorphism in the Japanese and suggest that a VDR-FokI polymorphism may affect bone mineral metabolism and can predict risk of osteoporosis as a complication of Graves' disease in patients in remission.
Thyroid 2000 May
PMID:Vitamin D receptor initiation codon polymorphism in Japanese patients with Graves' disease. 1088 83

Recent studies have shown that related genetic influences on bone mineral density (BMD) and bone turnover are related to allelic variations in the vitamin D receptor (VDR) gene. Osteoporosis as a complication of hyperthyroidism is characterized by increased rates of both bone formation and bone resorption. In addition, VDR gene polymorphism influences susceptibility to some autoimmune diseases such as insulin-dependent diabetes mellitus (IDDM) and multiple sclerosis (MS). In the gene encoding the VDR, we investigated the distribution of a VDR-FokI polymorphism that changes the predicted protein sequence. The subjects were 131 female Japanese patients with Graves' disease and 150 female controls. The distribution of genotype frequencies differs between Graves' disease and controls (chi2 = 5.99, degrees of freedom = 2, p = 0.0386). We found overexpression of F allele (69% vs. 61%, p = 0.0472) and homozygote FF (48% vs. 33%, p = 0.0118) in Graves' disease patients compared with controls. We also correlated a VDR-FokI polymorphism with BMD in the distal radius and biochemical markers of bone turnover in patients with Graves' disease in remission. Although generally, no significant association was seen between age-adjusted BMD and genotype, patients in remission for fewer than 5 years showed significantly lower age-adjusted BMD in Ff heterozygotes than in ff homozygotes (z = 1.14 ff vs. z = -0.43 Ff, p < 0.05). Moreover, serum concentrations of bone alkaline phosphatase were significantly greater in Ff homozygotes than in FF homozygotes (78 +/- 12 vs. 59 +/- 10, p < 0.05). The genotypes did not differ in serum concentrations of osteocalcin, urinary hydroxyproline, or urinary deoxypyridinoline. Our results indicate, for the first time, an association between Graves' disease and a VDR polymorphism in the Japanese and suggest that a VDR-FokI polymorphism may affect bone mineral metabolism and can predict risk of osteoporosis as a complication of Graves' disease in patients in remission.
Thyroid 2000 Jun
PMID:Vitamin D receptor initiation codon polymorphism in Japanese patients with Graves' disease. 1090 90

We have shown previously that continuous (6 days) intracerebroventricular (ICV) leptin infusion in normal rats resulted in decreases in food intake and body weight. A reduction of food intake imposed on control rats (pair-feeding), aimed at mimicking leptin-induced hyperphagia, produced a marked decrease in the expression of muscle uncoupling protein-3 (UCP-3), whereas ICV infusion of leptin prevented such a decrease in UCP-3. To investigate an involvement of thyroid hormones in this effect of leptin, plasma levels of these hormones were determined in ICV leptin-infused, ICV vehicle-infused ad libitum fed or pair-fed controls. ICV leptin infusion and pair-feeding resulted in decreased plasma thyroid-stimulating hormone (TSH) and T4 levels relative to ad libitum fed controls. ICV leptin infusion maintained plasma levels of T3, but the levels were decreased by pair-feeding. The activity of the enzyme (hepatic 5'-monodeiodinase) responsible for T4/T3 conversion was measured. In the leptin-infused group, the activity of 5'-monodeiodinase was maintained at the values measured in ad libitum fed rats; in pair-fed rats, activity was reduced. Thus, conversion of T4 to T3 is decreased by pair-feeding, whereas such is not the case during leptin infusion. To further substantiate an involvement of thyroid hormones in the effect of leptin on muscle UCP-3 expression, hypothyroid rats were ICV infused with leptin or vehicle. It was observed that in hypothyroid rats, ICV leptin was unable to maintain muscle UCP-3 expression at values measured in ad libitum fed controls. These results suggest that central leptin stimulates T3 production via an activation of T4 to T3 conversion, and that this stimulation could be responsible for the effect of leptin on muscle UCP-3 expression. Thyroid hormones could thus be important mediators of the effect of leptin on energy expenditure.
Diabetes 2000 Jul
PMID:Involvement of thyroid hormones in the effect of intracerebroventricular leptin infusion on uncoupling protein-3 expression in rat muscle. 1090 65

The objective of the present study was to determine the prevalence of autoimmune thyroid disease in Indian children with type 1 diabetes mellitus by the assay of antibodies to thyroid peroxidase and thyroglobulin. The study population consisted of 35 children with type 1 diabetes mellitus and 32 healthy age- and sex-matched control children. Thyroid peroxidase antibodies (TPO) were determined by ELISA and thyroglobulin antibodies (TGA) by passive hemagglutination. Thyroid function tests and tests of glycemic control were also performed. These assays were repeated after six months and one year. TPO were observed in 19 (54.3%) patients compared to three (10%) controls, and TGA in 11 (31.4%) patients and none of the controls. Both these observations were statistically significant with p=0.0002 for TPO and 0.0016 for TGA. The prevalence of these antibodies was not different in boys and girls and did not change with the duration of diabetes. All patients who were positive for TGA were also positive for TPO. Thyroid function tests were abnormal in one patient who was found to have Hashimoto's thyroiditis. There is a definite need to screen all diabetic children for thyroid antibodies and carefully follow up those patients in whom these antibodies are positive.
 ...
PMID:Autoimmune thyroid disease in Indian children with type 1 diabetes mellitus. 1130 45

Thyroid function tests might be affected by diabetes and obesity. To evaluate the influence of these parameters in routine conditions, 72 diabetic and 53 non-diabetic outpatients without known thyroid diseases or severe chronic illness were recruited over a 7-month period. For each patient, dosages of thyrotropin (TSH), total and free thyroxine (TT4 and FT4, respectively), total and free triiodothyronine (TT3 and FT3) and T3 resin uptake (T3RU) were performed by radioimmunoassays. The simultaneous influence of various parameters known to affect thyroid-function tests was evaluated by multivariate linear regression. The studied variables included gender, age, glucosteroids, estrogens, tobacco habits, iodine contacts, body mass index (BMI) and diabetes mellitus. Tobacco habits and iodine contacts did not influence any tests. As expected, estrogens induced an increase in TT4 and TT3 values (p < 0.001 and 0.020, respectively) associated with a decrease in T3RU (p < 0.001). Consequently, females had lower T3RU than males (p < 0.0001). Corticotherapy was associated with decreased TSH values (p = 0.022). TT3 and FT3 decreased with age (p < 0.001), whereas T3RU and FT4 increased (p = 0.020 and 0.004, respectively). In contrast to an increase in TSH (p = 0.006), TT4 and FT4 decreased at higher BMI levels (p = 0.018 and 0.004, respectively), which is consistent with subclinical hypothyroidism. In diabetic patients, TSH was lower than in nondiabetic subjects (p = 0.039). Thus, the present study indicates that besides known parameters such as age and drugs, thyroid-function tests can also be altered by diabetes mellitus and obesity.
 ...
PMID:Minor alterations in thyroid-function tests associated with diabetes mellitus and obesity in outpatients without known thyroid illness. 1138 17

Sex steroids have been reported to influence thyroid pathogenesis in human and experimental animals. However, there is no much report on the effect of sex steroids in the growth of normal thyroid. The present study is an attempt to know TSH-induced thyroid growth during sexual maturation in Wistar rats. Wistar rats of day 1 to day 150 postpartum (pp) were used in the present study. Thyroid growth indices such as absolute and relative thyroid weights, concentration of DNA in the thyroid, mitotic index and numerical density of thyrocytes, hormonal profiles in the serum and thyroid tissue such as thyrotropin (TSH), thyroid hormones, testosterone and estradiol, and receptors for TSH, androgen and estrogen in the thyroid were estimated. A gender-specific shift in the pattern of serum TSH and TSH-R was observed during 30-45 days of postnatal life, the period at which steroidogenesis by testes or ovaries of rats are reactivated. Testosterone in males and estradiol in females modulate thyroid growth through TSH. It is concluded from the present study that changes in the sex steroid status between male and female rats have a definite influence on the pattern of thyroid growth and TSH.
Exp Clin Endocrinol Diabetes 2002 Jan
PMID:Sex steroids regulate TSH-induced thyroid growth during sexual maturation in Wistar rats. 1183 24

Thyroid hormone action is an important determinant of energy and glucose metabolism. T4 metabolism is regulated by the deiodinases of which type 2 is expressed in humans in skeletal muscle and brown adipose tissue, where its transcription is stimulated by the beta-3 adrenergic pathway. We performed molecular scanning of the human type 2 deiodinase (DIO2) gene and evaluated a novel variant for associations with obesity and insulin resistance, assessing both the main effect and interaction with the Trp64Arg beta-3--adrenergic receptor (ADRB3) variant. Molecular scanning of DIO2 in 50 obese Caucasians demonstrated a Thr92Ala variant. Association studies in 972 nondiabetic patients, 135 of whom underwent euglycemic-hyperinsulinemic clamps, showed that subjects with the Thr92Ala variant had lower glucose disposal rate (0.54 plus minus 0.02 mg center dot min(-1) center dot kg(-1) fat-free mass Ala92 homozygotes vs. 0.44 plus minus 0.02 Ala92 heterozygotes vs. 0.42 plus minus 0.04 Thr92 homozygotes, P = 0.0088). Association analysis of the entire group showed significant evidence for a synergistic effect between the Thr92Ala DIO2 and Trp64Arg ADRB3 variants on BMI (both variants 34.3 plus minus 0.9 kg/m(2) vs. neither variant 33.1 plus minus 0.4 kg/m(2), P = 0.04 for interaction). To our knowledge, Thr92Ala is the first description of a missense mutation of DIO2. This variant strongly associates with insulin resistance and, in subjects with the Trp64Arg ADRB3 variant, an increased BMI, suggesting an interaction between these two common gene variants.
Diabetes 2002 Mar
PMID:Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. 1187 97

Orbital radiotherapy is a well-established method of treatment for severe Graves' ophthalmopathy, because of its anti-inflammatory and locally immunosuppressive effects. It has been used for 60 years. Conventional external x-ray and cobalt therapy have been abandoned, and most groups now use supervoltage linear accelerators (4-6 MeV). Cumulative doses may vary, but in most studies a cumulative dose of 20 Gy delivered over 2 weeks was utilized. Successful outcome depends on the selection of patients, because recent onset, active ophthalmopathy is much more favorably affected than longstanding, inactive disease. Inflammatory signs, recent onset eye muscle dysfunction, and optic neuropathy respond well to orbital radiotherapy, while proptosis and longstanding eye muscle restriction respond poorly. Overall, favorable responses have been reported, with few exceptions, in approximately 60% of cases. Combination of irradiation with high-dose systemic glucocorticoids provides better results than either treatment alone. Orbital radiotherapy is well tolerated and safe. Preexisting retinopathy (e.g., in patients with diabetes) is a contraindication to this treatment for the risk of further retinal damage. No case of radiation-induced tumors has so far been described after orbital radiotherapy for Graves' ophthalmopathy.
Thyroid 2002 Mar
PMID:Orbital radiotherapy for Graves' ophthalmopathy. 1195 48

The aim of this study was to investigate the frequency and mechanisms of hypothyroidism observed in diabetic patients with advanced diabetic nephropathy, including outcomes of management for this condition. A controlled study was designed using 32 diabetic and 31 non-diabetic patients not receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) who excreted mean urinary protein greater than 0.5 g/day examined on three consecutive days during admission to our hospital. Thyroid hormones in both serum and urine, anti-thyroid antibodies, renal function and iodine concentrations in serum were measured during admission in all patients included. In particular, in patients who showed overt hypothyroidism, further studies including large-needle biopsies of the thyroid and iodine-perchlorate discharge tests were performed. All patients in the two groups revealed negative antithyroid antibody titers, and the mean serum total iodine levels did not significantly differ between the two groups. Mean serum FT4 levels significantly decreased, and the TSH level was significantly elevated in the diabetic group compared to those in the non-diabetic group (p < 0.005, p < 0.02, respectively). The frequency of overt hypothyroidism in the diabetic group (22%; 7/32) was significantly higher (p < 0.05) than that in the non-diabetic group (3.2%; 1/31). The daily urinary thyroid hormone excretion in both groups did not show any significant correlation with serum thyroid hormone levels. Seven patients who revealed overt hypothyroidism in the diabetic group showed elevated serum total iodine levels during hypothyroidal status, ranging between 177 and 561 microg/l. Also, the iodine-perchlorate discharge tests carried out in six of these patients all showed a positive discharge. After management based on iodine restriction, normalization of serum thyroid hormone levels in accordance with definite decreases in the serum total iodine level was achieved, accompanied by a significant weight reduction. In conclusion, we found a significantly high prevalence of non-autoimmune primary hypothyroidism in patients with advanced diabetic nephropathy compared to those with non-diabetic chronic renal dysfunction, which may partly relate to earlier development of oedematous status. Clinical and laboratory findings suggest that impaired renal handling of iodine resulting in an elevation of serum iodine levels, rather than autoimmune mechanism or urinary hormone loss, may play a principal role in the development of these conditions, probably through a prolongation of the Wolff-Chaikoff effect. The mechanisms by which this phenomenon develops more frequently in diabetic than in non-diabetic renal dysfunction remain to be elucidated.
Exp Clin Endocrinol Diabetes 2002 Nov
PMID:Non-autoimmune primary hypothyroidism in diabetic and non-diabetic chronic renal dysfunction. 1251 52


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