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  • 1
    Electronic Resource
    Electronic Resource
    Subpopulations of antibodies directed against evolutionarily conserved regions of the insulin molecule in insulin-treated patients (1982)
    Springer
    Diabetologia 23 (1982), S. 488-493 
    Details
    ISSN: 1432-0428
    Keywords: Insulin antibodies ; insulin structure ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study, we attempted to define possible subpopulations of antibodies which theoretically could be directed against evolutionarily conserved regions of the insulin molecule in sera from insulin-treated diabetic patients using a variety of labelled and unlabelled insulins which differ widely in structure but are very similar in functional properties. Ten high titre human insulin antisera from patients treated with mixed beef-pork insulin were examined. All sera were found to bind 125I-pork insulin better than labelled chicken insulin which bound better than labelled fish insulin. Detailed studies were conducted with four of the antisera using the pork and fish tracers. With two of the antisera, a subpopulation of antibody could be detected with 125I-fish insulin which had similar affinity for both fish and pork insulin, but reacted much less well with guinea pig insulin and the desoctapeptide derivative of porcine insulin. Based on the known properties of these four insulins, the data provide suggestive evidence consistent with the hypothesis that there are subpopulations of antibodies recognizing regions on the insulin molecule that are well conserved, possibly the region involved in the formation of insulin dimers or receptor binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254296
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: identification of five novel polymorphisms (1996)
    Springer
    Diabetologia 39 (1996), S. 600-608 
    Details
    ISSN: 1432-0428
    Keywords: Insulin receptor substrate-1 (IRS-1) ; non-insulin-dependent diabetes mellitus ; genetics ; single-stranded conformation polymorphisms ; insulin resistance ; polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a potential candidate for development of non-insulin-dependent diabetes mellitus (NIDDM). In this study, we have identified IRS-1 gene polymorphisms, evaluated their frequencies in Japanese subjects, and analysed the contribution of these polymorphisms to the development of NIDDM. The entire coding region of the IRS-1 gene of 94 subjects (47 NIDDM and 47 control subjects) was screened by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) analysis. Seven SSCP polymorphisms were identified. These corresponded to two previously identified polymorphisms [Gly971→Arg (GGG→AGG) and Ala804 (GCA→GCG)] as well as five novel polymorphisms [Pro190→Arg (CCC→CGC), Met209→Thr (ATG→ACG), Ser809→Phe (TCT→TTT), Leu142 (CTT→CTC), and Gly625 (GGC→GGT)]. Although the prevalence of each of these polymorphisms was not statistically different between NIDDM and control subjects, the prevalence of the four IRS-1 polymorphisms with an amino acid substitution together was significantly higher in NIDDM than in control subjects (23.4 vs 8.5%, p〈0.05), and two substitutions (Met209→Thr and Ser809→Phe) were found only in NIDDM patients. Equilibrium glucose infusion rates during a euglycaemic clamp in NIDDM and control subjects with the IRS-1 polymorphisms decreased by 29.5 and 22.0%, respectively on the average when compared to those in comparable groups without polymorphisms, although they were not statistically significant. Thus, IRS-1 polymorphisms may contribute in part to the insulin resistance and development of NIDDM in Japanese subjects; however, they do not account for the major part of the decrease in insulin-stimulated glucose uptake which is observed in subjects with clinically apparent NIDDM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403308
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: identification of five novel polymorphisms (1996)
    Springer
    Diabetologia 39 (1996), S. 600-608 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin receptor substrate-1 (IRS-1) ; non-insulin-dependent diabetes mellitus ; genetics ; single-stranded conformation polymorphisms ; insulin resistance ; polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a potential candidate for development of non-insulin-dependent diabetes mellitus (NIDDM). In this study, we have identified IRS-1 gene polymorphisms, evaluated their frequencies in Japanese subjects, and analysed the contribution of these polymorphisms to the development of NIDDM. The entire coding region of the IRS-1 gene of 94 subjects (47 NIDDM and 47 control subjects) was screened by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) analysis. Seven SSCP polymorphisms were identified. These corresponded to two previously identified polymorphisms [Gly971→Arg (GGG→AGG) and Ala804 (GCA→GCG)] as well as five novel polymorphisms [Pro190→Arg (CCC→CGC), Met209→Thr (ATG→ACG), Ser809→Phe (TCT→TTT), Leu142 (CTT→CTC), and Gly625 (GGC→GGT)]. Although the prevalence of each of these polymorphisms was not statistically different between NIDDM and control subjects, the prevalence of the four IRS-1 polymorphisms with an amino acid substitution together was significantly higher in NIDDM than in control subjects (23.4 vs 8.5 %, p 〈 0.05), and two substitutions (Met209→Thr and Ser809→Phe) were found only in NIDDM patients. Equilibrium glucose infusion rates during a euglycaemic clamp in NIDDM and control subjects with the IRS-1 polymorphisms decreased by 29.5 and 22.0 %, respectively on the average when compared to those in comparable groups without polymorphisms, although they were not statistically significant. Thus, IRS-1 polymorphisms may contribute in part to the insulin resistance and development of NIDDM in Japanese subjects; however, they do not account for the major part of the decrease in insulin-stimulated glucose uptake which is observed in subjects with clinically apparent NIDDM. [Diabetologia (1996) 39: 600–608]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403308
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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