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)

Renal metabolism of amino acids (AAs) was evaluated in 5 patients with early IDDM, and in 7 controls (C) in the basal state for 80 minutes after the ingestion of an AA mixture simulating an animal protein meal. Insulin was withdrawn 20 hours before the study. Renal metabolism of AAs was evaluated by the arterial-venous difference technique. In the basal state in IDDM, as in C, the kidney takes up large amounts of a few nonessential AAs (NEAAs): it releases many NEAAs and a few essential AAs (EAAs). After AA ingestion in C, renal extraction of most EAAs, mainly BCAAs, Lys, and Thr, occurs; Pro extraction also increases and a significant uptake of Gly, Glu, Asp, Orn, and Tyr takes place. EAA extraction accounts for 30-40% of total AA uptake. In IDDM, after AA ingestion, a) renal uptake of total AAs is significantly lower, owing mainly to a markedly lower uptake of BCAAs, Lys, and also of Pro, Orn, and Ala; b) renal EAA uptake accounts for less than 20% of total AA extraction. These results indicate that in IDDM postprandial renal N repletion is impaired and unbalanced.
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PMID:Renal metabolism of amino acids in early insulin-dependent diabetes mellitus. 177 10

Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension. In addition, a polymorphism in the angiotensinogen gene substituting methionine for threonine (T174M) has been associated with hypertension in nondiabetic populations. We studied the relationship between these polymorphisms in the angiotensinogen gene in IDDM patients with diabetic nephropathy (121 men, 74 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years). There was no difference in M235T genotype distribution between IDDM patients with diabetic nephropathy and those with normoalbuminuria: 73/97/25 (37/50/13%) vs. 67/95/23 (36/52/12%) had MM/MT/TT genotypes, respectively. No difference in distribution of T174M genotypes between nephropathic and normoalbuminuric IDDM patients was observed either: 148/44/1 (77/23/0.5%) vs. 141/42/2 (76/23/1%) had TT/TM/MM genotypes, respectively. In patients with nephropathy, systolic blood pressure was higher (161 +/- 22 mmHg [mean +/- SD]) in patients carrying TT genotype of the M235T angiotensinogen polymorphism as compared with patients with MM or MT genotypes (150 +/- 23 mmHg; P = 0.03). We conclude that neither the M235T nor the T174M polymorphism in the angiotensinogen gene contributes to genetic susceptibility to diabetic nephropathy in white IDDM patients, whereas the TT genotype of the M235T is associated with elevated blood pressure in patients with diabetic nephropathy.
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PMID:Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy. 859 44

Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n = 242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n = 187); a geographically defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients with long duration of disease (> 15 years) and no evidence of overt nephropathy (n = 166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.
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PMID:Examination of two genetic polymorphisms within the renin-angiotensin system: no evidence for an association with nephropathy in IDDM. 887 96

The genetic susceptibility to Graves' disease and type 1 (insulin-dependent) diabetes mellitus is conferred by genes in the human leukocyte antigen region on the short arm of chromosome 6, but several other genes are presumed to determine disease susceptibility. Among those candidate genes is the cytotoxic T lymphocyte antigen 4 (CTLA4) located on chromosome 2q33 in man. We investigated the distribution of the CTLA4 exon 1 polymorphism (49 A/G) in Graves' disease and IDDM. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in the leader peptide of the expressed protein and was analyzed by PCR, single strand conformation polymorphism, and restriction fragment length polymorphism analysis in 305 patients with Graves' disease, 293 patients with IDDM, and 325 controls. Patients with Graves' disease had significantly more Ala alleles than controls, both as homozygotes (21% vs. 13%) and as heterozygotes (53% vs. 46%), and less Thr as homozygotes (26% vs. 42%; P < 2 x 10(-4). The phenotypic frequency of Ala-positive patients (73%) was significantly higher than of controls (58%; P = 10(-4); relative risk = 2). Patients with IDDM also had significantly more Ala alleles as homozygotes (19%) or heterozygotes (50%; P = 0.01). In conclusion, an alanine at codon 17 of CTLA4 is associated with genetic susceptibility to Graves' disease as well as to IDDM.
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PMID:CTLA4 alanine-17 confers genetic susceptibility to Graves' disease and to type 1 diabetes mellitus. 898 48

The molecular mechanism by which some, but not all, variants of encephalomyocarditis (EMC) virus selectively infect pancreatic beta-cells in mice and induce IDDM has been an enigma for more than a decade. We report here that the binding site of the EMC viral capsid protein VP1 determines viral diabetogenicity. Recombinant chimeric EMC viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 of the major capsid protein VP1 bind poorly to beta-cells. In contrast, recombinant chimeric EMC viruses containing alanine or glycine at position 152 of the VP1 bind efficiently to and infect beta-cells, resulting in the development of diabetes. Three-dimensional molecular modeling reveals that the van der Waals interactions are greater and the residues surrounding position 152 of the VP1 are more closely packed in recombinant chimeric viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 than in recombinant chimeric viruses containing alanine or glycine at the same position. Our studies reveal that the surface areas surrounding alanine or glycine at position 152 of the VP1 are more accessible, thus increasing the availability of the binding sites for attachment to beta-cell receptors and resulting in viral infection and the development of diabetes.
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PMID:Determination of encephalomyocarditis viral diabetogenicity by a putative binding site of the viral capsid protein. 956 90

NeuroD/BETA2, a transcription factor of the insulin gene, also plays an important role in the development of pancreatic beta-cells. Recently, the NeuroD/BETA2 gene has been mapped to the long arm of human chromosome 2 (2q32) where the IDDM7 gene has previously been mapped, implying its involvement in diabetes. To identify mutations in the NeuroD/BETA2 gene that may predispose patients to develop diabetes, we studied the gene in 50 Japanese subjects with diabetes (4 with type 1 and 46 with type 2) by the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism and sequencing analyses. Further analysis was performed in 392 Japanese subjects (60 with type 1 and 158 with type 2 diabetes and 174 healthy control subjects) by mismatch PCR restriction fragment length polymorphism. We found a DNA polymorphism of the NeuroD/BETA2 gene. A nucleotide G-to-A transition results in the substitution of alanine to threonine at codon 45 (Ala45Thr). The frequencies of heterozygotes for the Ala45Thr variant were 9.8% in the control subjects, 9.5% in the patients with type 2 diabetes, and 25.0% in the patients with type 1 diabetes, a significant difference (P = 0.006). Because the variant of the NeuroD/BETA2 gene (Ala45Thr) is associated with type 1 but not type 2 diabetes, it may be implicated in the loss of pancreatic beta-cells in type 1 diabetes.
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PMID:Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese. 1033 23

Recently, the association of CTLA4 gene polymorphism with type 1 diabetes and AITD has been reported in several populations. CTLA4 was originally reported to regulate T-cell activity and T-B cognate interaction. To investigate the role of CTLA4 in autoimmune diseases, we examined the correlation between CTLA4 gene polymorphism and the clinical characteristics of Japanese patients with type 1 diabetes, including the mode of onset of diabetes and presence of islet-specific autoantibodies (GAD, ICA 512 Ab) in the serum. We studied 111 patients with type 1 diabetes and 445 normal subjects. CTLA4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphism was defined, employing PCR-RFLP. Sixty-three (57%) patients had AITD. The allele frequencies of G and A in both 111 patients (G: 65%; A: 35%) and 63 patients (G: 62%; A: 38%) were not significantly different from the control subjects (G: 63%; A: 37%). Serum samples of 69 patients were obtained within a year after onset and used for pancreas specific autoantibodies analysis. These samples were also used for further analysis between CTLA4 gene polymorphism and clinical characteristics. The allele frequencies of G and A in patients who presented with diabetic ketoacidosis (DK+) (G: 75%; A: 25%) were significantly different from those in DK- patients (G: 50%, A: 50%, P = 0.003). Allele and genotype analyses showed significant differences between DK+ patients and control subjects (P = 0.014, P = 0.046, respectively). Allele frequencies of G and A were not significant between patients who were positive and negative for GAD Ab, but significant for ICA 512 Ab (G: 83%, A:17% versus G: 59%, A: 41%: positive patients versus negative patients, P = 0.004). Our results showed a significant correlation between CTLA4 gene polymorphism and ICA 512 Ab. Our results also indicated that CTLA4 gene polymorphism is associated with the onset mode of Japanese type 1 diabetes and the presence of ICA512 Ab. Further analysis of this polymorphism is necessary to fully understand the pathogenesis and progression of type 1 diabetes.
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PMID:CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 Ab in Japanese type 1 diabetes. 1072 97

Several studies have demonstrated an association of CTLA4 (IDDM12) alanine-17 with type 1 diabetes, but CTLA4 variants have not yet been investigated in type 2 diabetes. The CTLA4 exon 1 polymorphism (49 A/G) was analyzed in 300 Caucasian patients with type 2 diabetes and 466 healthy controls. All patients were negative for glutamate decarboxylase and islet cell antibodies. CTLA4 alleles were defined by PCR, single-strand conformational polymorphism, and restriction length fragment polymorphism analysis using BBV:I. The distribution of alleles as well as the genotypic and phenotypic frequencies were similar among patients and controls [AA, 42 vs. 39%; AG, 47 vs. 46%; GG, 11 vs. 15%, P = not significant (n.s.); A/G, 65/35% vs. 62/38%, P = n.s.; alanine/threonine 92/58% vs. 85/61%, P = n.s.]. However, detailed analysis of clinical and biochemical parameters revealed a tendency of GG (alanine/alanine) toward younger age at disease manifestation (46.8 +/- 0.8 vs. 49.5 +/- 0.8 yr, mean +/- SEM), lower body mass index (21.4 +/- 0.5 vs. 24.4 +/- 0.5 kg/m(2), P = 0.042), and basal C-peptide level (0.33 +/- 0.07 vs. 0.53 +/- 0.07nmol/L), as well as earlier start of insulin treatment (5.8 +/- 1.2 vs. 8.7 +/- 0.6 yr) and higher portion of patients on insulin (71 vs. 61%). Patients with the AA genotype were significantly less likely to develop microangiopathic lesions (P < 0.0005). No differences were found for hypertension or family history of type 2 diabetes. In conclusion, CTLA4 alanine-17 does not represent a major risk factor for type 2 diabetes. Additional studies on larger groups and different ethnic groups are warranted to clarify the association of the GG genotype with faster ss-cell failure and the lower rate of microvascular complications in AA carriers.
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PMID:The codon 17 polymorphism of the CTLA4 gene in type 2 diabetes mellitus. 1115 25

Platelet levels of 19 amino acids were measured in 20 outpatients with type 1 (age [mean +/- SE], 35.5 +/- 2.0 years) and 27 with type 2 (age, 58.4 +/- 1.4 years) diabetes, and 20 young (age 33.7 +/- 1.3 years) and 20 older (age 57.4 +/- 1.5 years) healthy volunteers. Platelet levels of most amino acids tended to be lower in patients with type 1 diabetes than in healthy controls. In particular, asparagine, glycine, taurine, alanine, valine, cysteine, leucine, phenylalanine, and lysine levels, expressed as nmol/10(8) platelets, were significantly lower. Only taurine significantly decreased in patients with type 2 diabetes, whereas threonine, alanine, and isoleucine increased.
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PMID:Preliminary report: Amino acid profile in platelets of diabetic patients. 1143 75

In type 2 diabetes, the threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with elevated fasting and postprandial triglycerides and dyslipidemia when compared with the wild type (Ala-54/Ala-54). To assess whether this is the case in patients with type 1 diabetes, who usually do not manifest the metabolic syndrome, we screened 181 patients with similar glycemic control as the type 2 patients. Thirty percent were heterozygous, and 9% were homozygous for the polymorphism. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild type (n = 84), those heterozygous for Ala-54/Thr-54 (n = 44), and those homozygous for the Thr-54 (n = 13) were 1.0 +/- 0.07, 1.1 +/- 0.17, and 1.2 +/- 0.23 mmol/liter, respectively. In addition, there were no differences in total, low-density lipoprotein, high-density lipoprotein, and non-high density lipoprotein cholesterol among the three groups. After a fat load, the postprandial area under the curve of triglyceride in plasma, chylomicrons, and very low-density lipoprotein were similar between the wild type (n = 18) and the Thr-54 homozygotes (n = 12). In conclusion, in contrast to type 2, type 1 diabetes does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene to cause hypertriglyceridemia/dyslipidemia. Insulin resistance could account possibly for this difference.
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PMID:Unlike type 2 diabetes, type 1 does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene. 1216 3


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