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)

1. A polyclonal, monospecific antibody to a constitutive, diabetes-inducible and insulin-reversible cytochrome P-450 isozyme (RLM6) was used to screen a male rat liver cDNA library in lambda gt 11. Six clones harbouring the RLM6 cDNA insert were isolated initially from the expression library and three of these were further plaque-purified and sub-cloned. A 1.1 Kb cDNA insert, representing approximately 65% of the expected full length cDNA was characterized by restriction endonuclease mapping and sequenced by the dideoxy chain-termination method. Comparison of the nucleotide sequence of RLM6 cDNA to that of ethanol-inducible P4502E1 rat cDNA showed the two cDNAs to be identical, the RLM6 cDNA corresponding to nucleotides 310-1402 of the P4502E1 sequence. 2. RLM6 cDNA probe was used in Northern blot and RNA dot blot hybridization analysis to demonstrate that both streptozotocin-induced diabetes and fasting significantly elevated the steady-state level of RLM6 mRNA in male rat liver. Increased RLM6 mRNA level in the diabetic rat resulted in increased RLM6 apoprotein synthesis when polysomal RNA was used in a cell-free, protein-synthesizing system, indicating that the elevated RLM6 level observed in diabetic rats was correlated directly with the increased RLM6 mRNA concentration. 3. Daily insulin treatment of diabetic rats reversed the diabetes-dependent increase in RLM6 mRNA in a time-dependent manner, returning to control values after approximately 2 weeks of continuous insulin treatment. This insulin-dependent decrease of the RLM6 mRNA level was paralleled by a similar time-dependent decrease in serum acetone concentration. 4. Treatment of the male diabetic rat with testosterone also resulted in a decrease in both RLM6 mRNA and in vitro translated apoprotein. 5. Modulation of RLM6 mRNA level in the diabetic rat by insulin and testosterone, and the nucleotide sequence similarity with that of P4502E1 confirms that diabetes-inducible P450RLM6 and ethanol-inducible P4502E1 are coded for by the same gene.
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PMID:Molecular cloning of a cDNA for rat diabetes-inducible cytochrome P450RLM6: hormonal regulation and similarity to the cytochrome P4502E1 gene. 144 86

HLA class II antigens are transmembrane glycosylated heterodimers composed of an alpha and a beta chain. Several of these chains are highly polymorphic. The structural bases of the polymorphism are nucleotide acid substitutions which are situated in the first domain (exon II) of alpha and beta genes. Specific sequences of these domains can be obtained by amplification of genomic DNA using the polymerase chain reaction. Polymorphic sites are recognized by restriction endonuclease treatment and separation of the DNA fragments by polyacrylamide gel electrophoresis. The resulting fragments of different lengths are used to identify different alleles. We used the above technique for typing the HLA-DQA1 alleles in 41 Tunisian diabetic patients. The frequency of DQA1*0301 was greatly increased compared with the control group. This was in agreement with previously published data in Caucasian and Japanese insulin-dependent diabetes mellitus (IDDM) patients, while the significant increase in the frequency of the DQA1*0501 allele was comparable with that of Caucasian IDDM patients but contrasted with a decrease in this allele in Japanese IDDM patients. Our results provide confirmation of the contribution of the DQA1*0301 allele to disease susceptibility in a Tunisian population.
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PMID:Association of type 1 diabetes mellitus with the HLA-DQA1*0301 allele in a Tunisian population. 168 Feb 41

In searching for a genetic marker of type 2 diabetes we estimated the frequency of alleles of the Bgl II restriction fragment length polymorphism (RFLP) of the insulin receptor gene in a group of type II diabetic patients (n = 50), characterized by OGTT (glucose, insulin, C-peptide) and insulin receptor binding parameters. Leucocyte DNA was incubated with restriction endonuclease Bgl II and specific fragments were determined by Southern blot technique, using radioactive plasmid pINSR 13.1 as insulin receptor gene probe for hybridization. Insulin receptor numbers and receptor affinity were estimated by 125I-(Tyr-A-14)- insulin binding to red blood cells. Among control subjects the 20 kb fragment (allele Bgl II+) had a frequency of 0.21. In our group of diabetic patients this allele had a frequency of 0.10 (n.s., p greater than 0.05). In our study the insulin receptor genotype had no influence on body mass index, insulin and C-peptide during OGTT as well as insulin receptor binding data. So far, etiopathogenetic linkage between diabetes and insulin receptor variants (mutants) could unambiguously be proved in patients with extreme insulin resistance only. In our opinion, the estimation of the role of the gene as the reason underlying the disease inevitably requires the investigation of large families with multiple occurrence of type 2 diabetes.
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PMID:Restriction fragment length polymorphism of the insulin receptor gene, type 2 diabetes and insulin binding. 168 Jul 59

Using two different techniques, phenotyping and genotyping, we have studied allelic variation at amino acids 112 and 158 of the apolipoprotein E gene locus in 52 patients with insulin-dependent diabetes and in 58 non-diabetic controls. Phenotypes were determined by isoelectric focusing and immunoblotting of delipidated, neuraminidase-treated plasma. Genotypes were determined by using the polymerase chain reaction to amplify a 227 base pair fragment of the apolipoprotein E gene spanning both allelic sites. This was then digested with the restriction endonuclease CfoI and the alleles identified by polyacrylamide gel electrophoresis. Discrepancies between phenotype and genotype were observed in 16 (15%) of the individuals studied, 7 (13%) in the diabetics and 9 (17%) in the controls. From these results it is concluded that isoelectric focusing can lead to the erroneous assignment of apolipoprotein E phenotype even after pretreatment with neuraminidase. It is suggested that genotyping by DNA analysis is the method of choice in determining apolipoprotein E status.
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PMID:Apolipoprotein E phenotyping: a word of caution. 177 11

To assess the contribution of the HepG2/erythrocyte glucose-transporter (HepG2 GT) gene to the inherited susceptibility to non-insulin-dependent diabetes mellitus (NIDDM), cDNA and genomic probes were used to search for restriction-endonuclease polymorphisms at this locus. Analysis of DNA from 16 unrelated Black American individuals with 19 enzymes and as many as six different probes, defined four polymorphisms over a 45-kilobase region. Nucleotide diversity (pi = 0.006) was low relative to that at other loci, with an average of 1 in 1700 base pairs different between two chromosomes at this locus. The observed combined heterozygosity for these four sites was 0.69, which indicates that the markers at this locus could be useful for linkage analysis in families. Linkage-disequilibrium values between the four polymorphisms were evaluated by pairwise analysis and extended haplotypes. Calculating pairwise associations by the disequilibrium statistic delta or by another measure of disequilibrium, D' (the maximum likelihood of disequilibrium, which is less dependent on frequency), significant linkage disequilibrium could not be demonstrated. However, the frequencies of the observed extended haplotypes were shown to differ (chi 2 = 9.1, df = 2, P less than 0.025) from predicted frequencies if the sites were in linkage equilibrium in Blacks. The frequencies of these four polymorphisms were determined in Black nondiabetic (n = 44) and NIDDM (n = 63) subjects. Neither the allelic nor genotypic frequencies of the polymorphisms differed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Jan
PMID:Polymorphisms of HepG2/erythrocyte glucose-transporter gene. Linkage relationships and implications for genetic analysis of NIDDM. 197 57

A cohort of 132 well-documented White Welsh non-insulin-dependent diabetic (NIDDM) subjects were genotyped for 5 restriction-fragment-length polymorphisms (RFLPs) at the insulin-receptor gene (IRG) locus and a polymorphic locus 5' to the insulin gene. There was no significant difference in RFLP frequencies between the NIDDM subjects and a group of 87 matched White control subjects. Paired haplotype analysis of the IRG RFLPs suggested a difference between NIDDM and control groups for the endonuclease combinations Bgl II-Rsa I and Bgl II-Xba I. Analysis of implied haplotypes defined by the endonucleases Bgl II, Rsa I, and Xba I revealed one haplotype to be more prevalent in the NIDDM group; whereas, another haplotype was associated with the control group (P less than 0.02). Subset analysis within the NIDDM cohort compared the metabolic response of NIDDM subjects with the differing IRG haplotypes to a standard meal tolerance test. Both groups showed equivalent basal and postprandial glucose excursions, but one group revealed a significantly exaggerated plasma insulin response compared with the other (P less than 0.05). This may reflect the influence of genetic variation at the IRG locus on insulin sensitivity in patients with NIDDM.
Diabetes 1990 Dec
PMID:Allelic variants at insulin-receptor and insulin gene loci and susceptibility to NIDDM in Welsh population. 197 26

Type I diabetes is strongly associated with the major histocompatibility complex (MHC) class II region (DR and DQ loci), and to a lesser extent the class III region (complement C4 loci). Restriction fragment length polymorphism analysis was employed to investigate the C4 and heat shock protein 70 (HSP70) loci of 176 patients with type I diabetes and 92 healthy controls. In the patient population there was an excess of deletions of the C4A locus (48.5% vs 22.1%, P less than 0.0005). The HSP70 probe in conjunction with the restriction endonuclease Pst I detects two alleles of 9 or 8.5 kilobases (kb). The 8.5 kb allele was significantly increased in the patient group compared to healthy controls (0.569 vs 0.353, respectively, P less than 0.0005). Furthermore, a C4A deletion nearly always occurred with the 8.5 kb HSP70 allele, suggesting that it may be a marker of the HLA-A1,B8,C4A deletion, DR3 extended haplotype.
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PMID:Complement C4 and heat shock protein 70 (HSP70) genotypes and type I diabetes mellitus. 227 64

Inheritance of insulin-dependent diabetes mellitus (IDDM) is polygenic, and at least one of the genes conferring susceptibility to diabetes is tightly linked to the MHC. Recent studies have suggested that DQB1 of humans and I-A beta of mice are closely associated with susceptibility and resistance to IDDM. For further characterization and localization of the MHC-linked diabetogenic gene, we studied the genomic sequence of the A beta gene of the nonobese diabetic (NOD) mouse, an animal model of IDDM, in comparison with those of its sister strains, nonobese nondiabetic and cataract Shionogi (CTS) mice, and the original strain, outbred Imperial Cancer Research (ICR) mice. Genomic DNAs from these strains were amplified in vitro by the polymerase chain reaction with thermostable Taq polymerase. The amplified sequences were analyzed by restriction endonuclease digestion, hybridization with allele-specific oligonucleotide probes, and direct sequencing. The unique I-A beta sequence of NOD mice was observed in the sister strain, CTS mice, and in one mouse of the original strain, outbred ICR mice. These data together with the results of MAb typing of MHC molecules and restriction mapping of the I-A region suggest that the unique class II MHC of NOD mice is not the result of a recent mutation, but is derived from the original strain. Since class I MHC of CTS mice is different from the MHC of NOD mice at both the K and D loci, CTS mice are a naturally occurring recombinant strain with NOD type class II MHC and non-NOD type class I MHC. Thus, breeding studies in crosses of NOD with CTS mice should provide biological information on whether the unique class II MHC of NOD mice is diabetogenic.
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PMID:Major histocompatibility complex-linked diabetogenic gene of the nonobese diabetic mouse. Analysis of genomic DNA amplified by the polymerase chain reaction. 229 94

Recently, we examined a restriction fragment length polymorphism (RFLP) at the insulin receptor locus in Mexican Americans. This RFLP can be detected using the restriction endonuclease Rsa I, and has three alleles of 3.4 kb, 6.2 kb, and 6.7 kb. Our data suggested that the 3.4 kilobase pair (kb) allele may be associated with type II (non-insulin dependent) diabetes mellitus in Mexican Americans. We initiated studies to identify additional polymorphisms at the insulin receptor locus that might be useful in further studies on the association of type II diabetes and the insulin receptor gene. During the course of these studies we observed that the 6.7 kb and 6.2 kb alleles of the RsaI polymorphism appears to be due to an insertion or deletion of DNA sequences, so that DNA fragments of different lengths are generated when DNA from heterozygous individuals is digested with selected restriction endonucleases that cut on either side of this region. The 3.4 kb allele is apparently due to a site specific polymorphism. In the present report, results of these findings are presented as well as a description of additional polymorphisms that we have identified among Mexican Americans.
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PMID:Restriction fragment length polymorphism of the human insulin receptor gene among Mexican Americans. 257 18

The gene frequencies of a polymorphism in the 5'-flanking region of the insulin gene and its relationship to cardiovascular disease risk were studied in a well defined population of children (mean age 5.5 years) from a biracial community. The BglII endonuclease was used for digestion of the DNA around this polymorphic region. The risk factors studied included parental and grandparental self-reported histories of myocardial infarction and diabetes mellitus, fasting glucose and insulin levels, lipoprotein, cholesterol, and triglyceride levels, and skinfold thicknesses and weight. Four alleles were observed at this locus, with the class 2 allele being significantly more common among blacks than whites. Among white children, the class 3 allele was associated with increased risk for grandparental diabetes mellitus. White children with 2 copies of the class 3 allele had significantly higher levels of glucose. Black children with a copy of the class 3 allele had significantly higher levels of insulin. This study indicates that the class 3 allele is potentially associated with risk for diabetes mellitus and coronary heart disease that can be observed in childhood.
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PMID:Polymorphism in the 5'-flanking region of the insulin gene and its potential relation to cardiovascular disease risk: observations in a biracial community. The Bogalusa Heart Study. 267 72


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