Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Linkage analysis of the glucokinase locus in familial Type 2 (non-insulin-dependent) diabetic pedigrees (1993)
    Springer
    Diabetologia 36 (1993), S. 141-145 
    Details
    ISSN: 1432-0428
    Keywords: Familial Type 2 (non-insulin-dependent) diabetes mellitus linkage analysis ; glucokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucokinase is among the few genes which may play a key role in both insulin secretion and insulin action. Glucokinase is present in pancreatic beta cells where it may have a key role in the glucose sensing mechanism, and it is present in hepatocytes, where it may participate in glucose flux. Glucokinase defects have recently been implicated in maturity-onset diabetes of the young. To examine the hypothesis that glucokinase plays a key role in the predisposition to common familial Type 2 (non-insulin-dependent) diabetes mellitus, we typed 399 members of 18 Utah pedigrees with multiple Type 2 diabetic individuals for two markers in the 5′ and 3′ flanking regions of the glucokinase gene. Linkage analysis was performed under both dominant and recessive models. We also repeated these analyses with individuals with impaired glucose tolerance who were considered affected if their stimulated (2-h) glucose exceeded age-specific normal levels for 95 % of the population. Under several dominant models, linkage was significantly excluded, and under recessive models log of the odds (LOD) score was less than −1. We were also unable to demonstrate statistical support for the hypothesis that a small subgroup of pedigrees had glucokinase defects, but the most suggestive pedigree (individual pedigree LOD 1.8–1.9) ranked among the youngest and leanest in our cohort. We can exclude a major role for glucokinase in familial Type 2 diabetes, but our data cannot exclude a role for this locus in a minority of pedigrees. Further testing of the hypothesis that glucokinase defects contribute to diabetes in a small proportion of Type 2 diabetic pedigrees must await thorough sequence analysis of the glucokinase gene, including regulatory regions, particularly from pedigrees with positive LOD scores.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400695
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Glucokinase gene in gestational diabetes mellitus: population association study and molecular scanning (1994)
    Springer
    Diabetologia 37 (1994), S. 104-110 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; glucokinase ; gestational diabetes ; American Blacks ; single-strand conformation polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mutations of the glucokinase gene result in early-onset familial Type 2 (non-insulin-dependent) diabetes mellitus, and several members of the mutant glucokinase kindreds were originally diagnosed as having gestational diabetes. This study examined the glucokinase gene in 270 American Black women, including 94 with gestational diabetes whose diabetes resolved after pregnancy (gestational diabetes only), 77 with gestational diabetes who developed Type 2 diabetes after pregnancy (overt diabetes), and 99 normal control subjects who were recruited during the peripartum period. Two simple sequence repeat polymorphisms flanking either end of the glucokinase gene were evaluated. No association was found between glucokinase alleles and gestational diabetes only or overt diabetes, after adjustment for multiple comparisons. To detect single base changes, all 11 exons and proximal islet and liver promoter regions were examined by polymerase chain reaction plus single-stranded conformational polymorphism analysis in 45 gestational diabetes only patients who had not yet developed Type 2 diabetes. Nine coding region variants were identified: Ala11 (GCC) to Thr11 (ACC) in islet exon 1, and 8 variants either in untranslated regions or in the third base of a codon. Four variant sites were found in introns, but none in splicing consensus sequences. Analysis of the promoter regions revealed two common variants, G→A at islet −30 (24%), and G→A at liver −258 (42%). The frequencies of the promoter variants, determined by allele specific polymerase chain reaction analysis, did not differ among the three groups. Thus, no significant coding sequence glucokinase mutations were found in 90 alleles from 45 patients with gestational diabetes. Further studies will be required to rule out a minor role of the newly-described promoter region variants as susceptibility factors in this disorder.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428785
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    A genetic marker at the glucokinase gene locus for Type 2 (non-insulin-dependent) diabetes mellitus in Mauritian Creoles (1992)
    Springer
    Diabetologia 35 (1992), S. 632-638 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; glucokinase ; population association study ; polymorphism ; dinucleotide (CA)n repeat ; obesity ; genetic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence of Type 2 (non-insulin-dependent) diabetes mellitus is high in Mauritius, a multiethnic island nation in the southwestern Indian Ocean. Evaluation of candidate genes in the different ethnic groups represents a means of assessing the genetic component. As glucokinase is known to be a key regulator of glucose homeostasis in liver and pancreatic Beta-cells, the human gene was isolated and a dinucleotide repeat (CA)n marker was identified at this locus. A polymerase chain reaction assay was developed, and alleles differing in size were observed in individuals, according to the number of repeats in the amplified fragment. Eighty-five Creoles and 63 Indians of known glucose tolerance status were typed by amplification of genomic DNA for this dinucleotide (CA)n repeat marker. Four different alleles were observed including Z, the most common allele, and Z+2, Z+4, and Z+10, which differed from Z by 2, 4, and 10 nucleotides respectively. In Mauritian Creoles, the frequency of the Z+2 allele was greater in Type 2 diabetic subjects than in control subjects (23.8 % vs 8.9 %, p=0.008), and the frequency of the Z allele was lower in Type 2 diabetic subjects (60% vs 75.6%, p=0.03). Analysis with univariate logistic regression models indicated that the Z+2 allele had the highest odds ratio, 3.08 (95% confidence interval 1.14–8.35, p=0.0416), among the other risk factors (age, sex, body mass index, and waist/hip ratio). The multivariate odds ratio for Type 2 diabetes was 2.88 (95% confidence interval 0.98–8.50, p=0.0551). In contrast, in the Mauritian Indian population, no differences were noted between the frequency of any glucokinase allele in the Type 2 diabetic and control groups. These data suggest that the Z+2 allele is an important risk factor for Type 2 diabetes in Mauritian Creoles, but not in Mauritian Indians, and also imply that the glucokinase gene may play a role in the pathogenesis of Type 2 diabetes in Mauritian Creoles. Further studies are needed to define the nature of this defect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400254
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Two microsatellite repeat polymorphisms flanking opposite ends of the human glucokinase gene: use in haplotype analysis of Welsh Caucasians with Type 2 (non-insulin-dependent) diabetes mellitus (1993)
    Springer
    Diabetologia 36 (1993), S. 409-413 
    Details
    ISSN: 1432-0428
    Keywords: Glucokinase gene ; microsatellite ; polymorphism ; linkage disequilibrium ; haplotypes ; Type 2 (non-insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to evaluate the role of potential glucokinase defects contributing to susceptibility to Type 2 (non-insulin-dependent) diabetes mellitus in Welsh Caucasians. For this analysis, two microsatellite repeat polymorphisms flanking opposite ends of the gene were employed. For a recently described microsatellite (GCK2), located 6 kilobases upstream of islet exon 1, six different sized alleles were observed, with heterozygosity of 0.50 and polymorphism information content 0.44. Combined heterozygosity with another microsatellite repeat (GCK1) was 0.72. Significant linkage disequilibrium was noted between GCK2 and GCK1, suggesting that haplotypes may be a better predictor of Type 2 diabetes than analysis with either microsatellite alone. Using these two markers, the association with Type 2 diabetes was examined. The frequencies of alleles and genotypes at GCK1 did not differ between the patients with Type 2 diabetes (n=157) and control subjects (n=73). Similarly no differences were observed in GCK2 alleles or genotypes. The frequencies of haplotypes, derived from the two markers, also did not differ between the two groups. To investigate the possibility of minor metabolic effects of glucokinase defects, we also studied the association between the GCK alleles or haplotypes and the response profiles to meal tolerance tests. No association was observed between plasma glucose or insulin responses to meal tolerance tests with GCK haplotypes or alleles. These results suggest that glucokinase mutations in Welsh Caucasians are not major determinants of susceptibility to the common type of Type 2 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402276
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Variability of the pancreatic islet beta cell/liver (GLUT 2) glucose transporter gene in NIDDM patients (1994)
    Springer
    Diabetologia 37 (1994), S. 420-427 
    Details
    ISSN: 1432-0428
    Keywords: NIDDM ; glucose transporter ; allele ; genotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of these experiments was to test the hypothesis that impaired glucose-stimulated insulin secretion in NIDDM is due to mutations in the islet beta cell/liver glucose transporter (GLUT 2) gene. Using oligonucleotide primers flanking each of the 11 exons, the structural portion of the gene was studied by PCR-SSCP analysis. DNA from African-American females (n=48), who had gestational diabetes but developed overt NIDDM after delivery, was studied. Each SSCP variant was sequenced directly from genomic DNA. Two amino acid substitutions from the previously reported sequence were found, one in exon 3 and the other in exon 4 B. Four additional silent mutations in the coding region, and six intron mutations outside the splice junction consensus sequences, were also identified. The mutation GTC x ATC in exon 4B substituted Val197 to Ile197. This amino acid substitution was found in only one NIDDM patient in a single allele, and was not found in 52 control subjects. This residue exists in the fifth membrane spanning domain, and Val at this position is conserved in mouse and rat GLUT 2, and human GLUT 1 to GLUT 4. The other codon change in exon 3, ACT x ATT, substituted Thr110 to Ile110 in the second membrane spanning domain. To determine the frequency of this non-conservative amino acid substitution, a PCR-LCR assay was developed. This assay was simple and highly specific for detection of this single nucleotide substitution. The allelic frequency of the ATT (Ile110) in NIDDM patients (39.6%, n=48) and that in controls (47.1%, n=52) did not differ (p=0.32, Fisher's exact test). In conclusion, we identified two variant GLUT 2 glucose transporters in a subset of NIDDM patients. The rare variant in exon 4 B may contribute to the diabetic susceptibility and awaits further investigation. However, structural abnormalities of the GLUT 2 transporter associated with NIDDM appeared to be rare and were not likely to be a major determinant of genetic susceptibility to this type of diabetes in the population studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408481
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Glucokinase gene in gestational diabetes mellitus: population association study and molecular scanning (1994)
    Springer
    Diabetologia 37 (1994), S. 104-110 
    Details
    ISSN: 1432-0428
    Keywords: Key words Type 2 (non-insulin-dependent) diabetes mellitus, glucokinase, gestational diabetes, American Blacks, single-strand conformation polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mutations of the glucokinase gene result in early-onset familial Type 2 (non-insulin-dependent) diabetes mellitus, and several members of the mutant glucokinase kindreds were originally diagnosed as having gestational diabetes. This study examined the glucokinase gene in 270 American Black women, including 94 with gestational diabetes whose diabetes resolved after pregnancy (gestational diabetes only), 77 with gestational diabetes who developed Type 2 diabetes after pregnancy (overt diabetes), and 99 normal control subjects who were recruited during the peripartum period. Two simple sequence repeat polymorphisms flanking either end of the glucokinase gene were evaluated. No association was found between glucokinase alleles and gestational diabetes only or overt diabetes, after adjustment for multiple comparisons. To detect single base changes, all 11 exons and proximal islet and liver promoter regions were examined by polymerase chain reaction plus single-stranded conformational polymorphism analysis in 45 gestational diabetes only patients who had not yet developed Type 2 diabetes. Nine coding region variants were identified: Ala11 (G CC) to Thr11 (A CC) in islet exon 1, and 8 variants either in untranslated regions or in the third base of a codon. Four variant sites were found in introns, but none in splicing consensus sequences. Analysis of the promoter regions revealed two common variants, G→A at islet −30 (24 %), and G→A at liver −258 (42 %). The frequencies of the promoter variants, determined by allele specific polymerase chain reaction analysis, did not differ among the three groups. Thus, no significant coding sequence glucokinase mutations were found in 90 alleles from 45 patients with gestational diabetes. Further studies will be required to rule out a minor role of the newly-described promoter region variants as susceptibility factors in this disorder. [Diabetologia (1994) 37: 104–110]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050079
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Variability of the pancreatic islet beta cell/liver (GLUT 2) glucose transporter gene in NIDDM patients (1994)
    Springer
    Diabetologia 37 (1994), S. 420-427 
    Details
    ISSN: 1432-0428
    Keywords: Key words: NIDDM, glucose transporter, allele, genotype.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of these experiments was to test the hypothesis that impaired glucose-stimulated insulin secretion in NIDDM is due to mutations in the islet beta cell/liver glucose transporter (GLUT 2) gene. Using oligonucleotide primers flanking each of the 11 exons, the structural portion of the gene was studied by PCR-SSCP analysis. DNA from African-American females (n =48), who had gestational diabetes but developed overt NIDDM after delivery, was studied. Each SSCP variant was sequenced directly from genomic DNA. Two amino acid substitutions from the previously reported sequence were found, one in exon 3 and the other in exon 4 B. Four additional silent mutations in the coding region, and six intron mutations outside the splice junction consensus sequences, were also identified. The mutation GTC×ATC in exon 4 B substituted Val197 to Ile197. This amino acid substitution was found in only one NIDDM patient in a single allele, and was not found in 52 control subjects. This residue exists in the fifth membrane spanning domain, and Val at this position is conserved in mouse and rat GLUT 2, and human GLUT 1 to GLUT 4. The other codon change in exon 3, ACT×ATT, substituted Thr110 to Ile110 in the second membrane spanning domain. To determine the frequency of this non-conservative amino acid substitution, a PCR-LCR assay was developed. This assay was simple and highly specific for detection of this single nucleotide substitution. The allelic frequency of the ATT (Ile110) in NIDDM patients (39.6 %, n =48) and that in controls (47.1 %, n =52) did not differ (p =0.32, Fisher's exact test). In conclusion, we identified two variant GLUT 2 glucose transporters in a subset of NIDDM patients. The rare variant in exon 4 B may contribute to the diabetic susceptibility and awaits further investigation. However, structural abnormalities of the GLUT 2 transporter associated with NIDDM appeared to be rare and were not likely to be a major determinant of genetic susceptibility to this type of diabetes in the population studied. [Diabetologia (1994) 37: 420–427]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00408481
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Molecular screening of the glucokinase gene in familial Type 2 (non-insulin-dependent) diabetes mellitus (1994)
    Springer
    Diabetologia 37 (1994), S. 182-187 
    Details
    ISSN: 1432-0428
    Keywords: Key words Familial Type 2 (non-insulin-dependent) diabetes mellitus, molecular screening, single strand conformation polymorphisms, glucokinase gene.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The glucokinase locus has been implicated by linkage studies in several Caucasian pedigrees with early onset, autosomal dominant diabetes, and mutations have been identified in a large number of these pedigrees. Although mutations have been reported in some pedigrees with late onset Type 2 (non-insulin-dependent) diabetes mellitus, linkage studies of typical familial Type 2 diabetes did not suggest a major role for this locus. Nonetheless, linkage studies were consistent with the hypothesis that mutations of the glucokinase gene were responsible for the pathogenesis of Type 2 diabetes in a minority of pedigrees or one gene in a polygenic disorder. To systematically address this hypothesis, we examined 60 diabetic members of 18 pedigrees ascertained for two or more Type 2 diabetic siblings and eight unrelated diabetic spouses. Initially, the coding regions from each of the 11 glucokinase exons were examined by the sensitive technique of single strand conformation polymorphism analysis to screen for single nucleotide substitutions. Subsequently, we also sequenced each exon from an affected member of the single pedigree in which a glucokinase allele was most likely to segregate with diabetes. Single strand conformation polymorphism analysis detected only three variants, none of which altered the amino acid sequence. No coding or splice site mutations were detected. Likewise, no additional mutations were detected upon direct sequence analysis. However, additional screening of promoter and 3′ untranslated regions detected a variant pattern in the untranslated region of exon 10 which appeared to segregate with diabetes and impaired glucose tolerance in one pedigree. Sequence analysis demonstrated the deletion of a cytosine in exon 10 at position 906, but this deletion was not associated with Type 2 diabetes among unrelated spouses, was not linked to diabetes, and was not associated with significant elevations of fasting glucose or insulin among non-diabetic pedigree members. Similarly, two common variants in the islet promoter did not segregate with diabetes. We conclude that among typical familial Type 2 diabetes in a population representative of Northern European Caucasians, glucokinase mutations are an unlikely cause of diabetes. [Diabetologia (1994) 37: 182–187]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050091
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    5-tert-Butyladamantan-2-one (1983)
    s.l. : American Chemical Society
    The @journal of organic chemistry 48 (1983), S. 1099-1101 
    Details
    ISSN: 1520-6904
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jo00155a034
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    Pyrolysis of volatile aromatic hydrocarbons and n-heptane over calcium oxide and quartz (1985)
    s.l. : American Chemical Society
    Industrial and engineering chemistry 24 (1985), S. 1080-1087 
    Details
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/i200031a031
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...