Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (non-insulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2 Kb or 3.6 Kb. The frequency of the 6.7 Kb band was less than that in Caucasians. Furthermore, 15% of all the Japanese subjects examined lacked a 3.6 Kb band, which is commonly found in Caucasians. We have also detected restriction fragment length polymorphism in the human insulin receptor gene by Pvu II or Stu I digestion. Although no significant association of restriction fragment length polymorphism with Type 2 diabetes was found in the present study, our results suggest that the restriction fragment length polymorphism in the human insulin receptor gene varies among ethnic groups, and that the restriction fragment length polymorphism linked to the human insulin receptor gene might be a useful marker for the linkage study of the genes located close to the human insulin receptor gene on chromosome 19.
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PMID:Restriction fragment length polymorphism (RFLP) of the human insulin receptor gene in Japanese: its possible usefulness as a genetic marker. 287 50

Genotypes identified by two restriction fragment length polymorphisms (RFLPs) of the insulin receptor gene (IRG) with the restriction endonuclease Sst-1 were determined in a Japanese group comprising 51 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 50 control subjects. Southern hybridization using a probe for the beta subunit of the human IRG identifies 4 alleles, termed S1(+) (5.3 kb), S1(-) (5.8 kb), S2(+) (7.0 and 2.4 kb) and S2(-) (9.4 kb). The frequencies of genotypes possessing the S1(-) allele in Japanese controls and Japanese NIDDM patients were 0.11 and 0.16, respectively. Unlike the previously reported association of the S1(-) allele with NIDDM found in Caucasians there was no significant difference in the frequency of the S1(-) allele between non-diabetic and NIDDM Japanese patients. There was a significant difference in the frequency of the S2(+) allele between Caucasian control subjects (0.14) and Japanese controls (0.0) and NIDDM patients (0.02).
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PMID:DNA polymorphisms of the insulin receptor gene in Japanese subjects with non-insulin-dependent diabetes mellitus. 290 2

We have identified a patient with mild diabetes, marked fasting hyperinsulinemia (89 to 130 microU of insulin per milliliter), and a reduced fasting C-peptide: insulin molar ratio of 1.11 to 1.50 (normal, greater than 4). The patient responded normally to exogenous insulin. However, her endogenous immunoreactive insulin showed reduced biologic activity during a glucose-clamp study with hyperglycemia and a reduced ability to bind to the insulin receptor and stimulate glucose transport in vitro. Family studies showed that five additional relatives in three generations had variable degrees of glucose intolerance, marked hyperinsulinemia, and a reduced peripheral C-peptide:insulin molar ratio. Restriction-endonuclease cleavage of DNA isolated from circulating leukocytes in the patient and in family members with hyperinsulinemia revealed loss of the MboII recognition site in one allele of the insulin gene--consistent with a point mutation at position 24 or 25 in the insulin B chain. Other studies using high-pressure liquid chromatography and detailed gene analysis have identified the defect as a serine for phenylalanine substitution at position 24 of the insulin B chain. The secretion of a structurally abnormal insulin should be considered in patients with hyperinsulinemia who respond normally to exogenous insulin and have a reduced C-peptide:insulin molar ratio. Glucose tolerance may range from relatively normal to overtly diabetic.
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PMID:Familial hyperinsulinemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome. 637 26

A patient with leprechaunism associated with severe insulin resistance was studied to identify the molecular and genetic basis for insulin resistance. Insulin binding and surface labeling of transformed lymphocytes prepared from the patient showed a significantly decreased insulin receptor number on the cell surface. Southern blot analysis of the insulin receptor gene showed no evidence of large insertions or deletions. Furthermore, direct sequencing of all 22 exons and exon-intron junctions of the insulin receptor gene failed to show any missense mutations, nonsense mutations, or mutations at exon-intron junctions. However, Northern blot analysis indicated significantly decreased insulin receptor mRNA expression in the patient's cells. Moreover, restriction endonuclease digestion of the amplified cDNA suggested that the expression levels of one allele were less efficient than the other. These findings suggested that the regulatory region of the insulin receptor gene might have abnormalities. Therefore, we examined the 5' flanking region of the insulin receptor gene. Southern blot analysis showed no major deletions or insertions between positions -1,823 and -2 relative to the translation initiation site. A 5' flanking region of the insulin receptor gene spanning positions -881 approximately +7 was amplified by polymerase chain reaction (PCR) and introduced into a reporter plasmid carrying the human growth hormone (hGH) gene. The nucleotide sequence of the amplified fragment showed two polymorphic sites at positions -603 and -500 in the patient, as well as in normal subjects. No other abnormal sequence was found in the patient. Promoter activity measured by hGH expression in transfected mouse L cells was not influenced by the polymorphism at position -603 located in a cluster of GC boxes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amplification and analysis of promoter region of insulin receptor gene in a patient with leprechaunism associated with severe insulin resistance. 753 83

Aurintricarboxylic acid (ATA), an endonuclease inhibitor, prevents the death of a variety of cell types in culture. Previously we have shown that ATA, similar to insulin-like growth factor I (IGF-I), protected MCF-7 cells against apoptotic death induced by the protein synthesis inhibitor cycloheximide. Here we show that ATA and a polysulfonated aromatic compound, Evans blue (EB), similar to IGF-I, promote survival and increase proliferation of MCF-7 cells in serum-free culture medium. This may suggest a common signaling pathway shared by the aromatic polyanions and IGF-I. Therefore, the ability of these aromatic compounds to activate the signal transduction pathway of IGF-I was examined. We found that ATA and EB mimicked the IGF-I effect on tyrosine phosphorylation of the IGF-I receptor (IGF-IR) and its major substrates, insulin receptor substrate-1 (IRS-1) and IRS-2; induced the association of these substrates with phosphatidylinositol 3-kinase and Grb2; and activated Akt kinase and p42/p44 mitogen-activated protein kinases. ATA and EB competed for IGF-I binding to the IGF-IR. ATA was found to be selective for the IGF-IR, whereas EB also activated the insulin receptor. Upon fractionation of commercial ATA by size exclusion chromatography, we found that fractions that enhanced the intensity of tyrosyl-phosphorylated IRS-1/IRS-2 also increased the survival of MCF-7 cells in the presence of cycloheximide, whereas fractions devoid of IRS phosphorylation activity had no survival ability. Taken together, these results suggest that the survival/proliferation-promoting effects of ATA and EB in MCF-7 cells are transduced via the IGF-IR signaling pathway.
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PMID:Activation of the insulin-like growth factor 1 signaling pathway by the antiapoptotic agents aurintricarboxylic acid and evans blue. 1141 32

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