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  • candidate gene analysis  (2)
  • insulin sensitivity  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Variant sequences of the Hexokinase II gene in familial NIDDM (1996)
    Springer
    Diabetologia 39 (1996), S. 322-328 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Hexokinase II ; candidate gene analysis ; insulin resistance ; familial non-insulin-dependent diabetes mellitus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Hexokinase II (HKII) plays a central role in the intracellular metabolism of glucose in skeletal muscle, catalysing the phosphorylation of glucose to glucose 6-phosphate. It is therefore considered to be a potentially important candidate gene in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to screen the HKII gene for mutations in NIDDM subjects from insulin-resistant families. Insulin sensitivity was assessed in unaffected first degree relatives from families with two or more living NIDDM subjects, and 15 families were identified as being insulin resistant. In 15 NIDDM subjects (one from each family) and 4 normoglycaemic control subjects, all 18 exons of the HKII gene were amplified by the polymerase chain reaction, and the products screened for mutations using a combination of single-stranded conformational polymorphism analysis and direct sequencing. Six sequence variations were detected in the NIDDM subjects; four silent polymorphisms [GAT vs GAC at codon 251 in exon 7, AAT vs AAC at codon 692 in exon 15, CCG vs CCC at codon 736 in exon 15, and CTG vs CTA at codon 766 in exon 16]; a single base change [T→C], 22 base pairs distal to the exon-intron junction of exon 17 in the 5′-splice donor; and a single amino acid substitution [Gln142→His] in exon 4, which was identified in 6 of the 15 NIDDM subjects. The frequency of the mutated codon 142 allele however, was comparable between NIDDM subjects with familial NIDDM (n=56) and normoglycaemic control subjects (n=48) (18.8% and 14.6% for NIDDM subjects and control subjects respectively; χ2=0.6, p〉0.25). In addition, measures of insulin sensitivity were comparable in normal glucose tolerant subjects with (n=20) and without (n=40) the codon 142 polymorphism. In conclusion: (1) mutations in the coding regions of the HKII gene are unlikely to be major determinants in the development of insulin resistance and familial NIDDM; although (2) the influence of the codon 142 mutation in combination with other abnormalities of the insulin-signalling pathway on insulin action remain to be addressed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00418348
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 2
    Digitale Medien
    Digitale Medien
    Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance (1995)
    Springer
    Diabetologia 38 (1995), S. 699-704 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Key words Impaired glucose tolerance ; insulin sensitivity ; hepatic glucose output ; insulin secretion ; labelled infusion technique.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Recent evidence suggests that the postprandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (Δ 0–10 min insulin area 7 Δ 0–10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2–19.4] vs 9.1 [2.6–14.5] mU · mmol−1; p 〈 0.01). During the clamp, circulating insulin (93 ± 8 [mean ± SEM] and 81 ± 10 mU · l−1) and glucagon (54 ± 4 and 44 ± 6 ng · l−1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 ± 0.27 vs 4.47 ± 0.53 mg · kg−1· min−1; p 〈 0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38 ± 0.10 and 0.30 ± 0.18 mg · kg−1· min−1). Therefore, the main defects in subjects with impaired glucose tolerance are decreased first phase insulin secretion and peripheral non-oxidative glucose disposal, but hepatic glucose output shows normal responsiveness to insulin. [Diabetologia (1995) 38: 699–704]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00401842
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 3
    Digitale Medien
    Digitale Medien
    Variant sequences of the Hexokinase II gene in familial NIDDM (1996)
    Springer
    Diabetologia 39 (1996), S. 322-328 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Keywords Hexokinase II ; candidate gene analysis ; insulin resistance ; familial non-insulin-dependent diabetes mellitus.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Hexokinase II (HKII) plays a central role in the intracellular metabolism of glucose in skeletal muscle, catalysing the phosphorylation of glucose to glucose 6-phosphate. It is therefore considered to be a potentially important candidate gene in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to screen the HKII gene for mutations in NIDDM subjects from insulin-resistant families. Insulin sensitivity was assessed in unaffected first degree relatives from families with two or more living NIDDM subjects, and 15 families were identified as being insulin resistant. In 15 NIDDM subjects (one from each family) and 4 normoglycaemic control subjects, all 18 exons of the HKII gene were amplified by the polymerase chain reaction, and the products screened for mutations using a combination of single-stranded conformational polymorphism analysis and direct sequencing. Six sequence variations were detected in the NIDDM subjects; four silent polymorphisms [GAT vs GAC at codon 251 in exon 7, AAT vs AAC at codon 692 in exon 15, CCG vs CCC at codon 736 in exon 15, and CTG vs CTA at codon 766 in exon 16]; a single base change [T→C], 22 base pairs distal to the exon-intron junction of exon 17 in the 5 ′-splice donor; and a single amino acid substitution [Gln142→His] in exon 4, which was identified in 6 of the 15 NIDDM subjects. The frequency of the mutated codon 142 allele however, was comparable between NIDDM subjects with familial NIDDM (n = 56) and normoglycaemic control subjects (n = 48) (18.8 % and 14.6 % for NIDDM subjects and control subjects respectively; χ 2 = 0.6, p 〉 0.25). In addition, measures of insulin sensitivity were comparable in normal glucose tolerant subjects with (n = 20) and without (n = 40) the codon 142 polymorphism. In conclusion: (1) mutations in the coding regions of the HKII gene are unlikely to be major determinants in the development of insulin resistance and familial NIDDM; although (2) the influence of the codon 142 mutation in combination with other abnormalities of the insulin-signalling pathway on insulin action remain to be addressed. [Diabetologia (1996) 39: 322–328]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00418348
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
  • 4
    Digitale Medien
    Digitale Medien
    Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance (1995)
    Springer
    Diabetologia 38 (1995), S. 699-704 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Impaired glucose tolerance ; insulin sensitivity ; hepatic glucose output ; insulin secretion ; labelled infusion technique
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Recent evidence suggests that the post-prandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (Δ 0–10 min insulin area ÷Δ 0–10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2–19.4] vs 9.1 [2.6–14.5] mU·mmol−1; p〈0.01). During the clamp, circulating insulin (93±8 [mean±SEM] and 81±10 mU·l−1) and glucagon (54±4 and 44±6 ng·l−1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78±0.27 vs 4.47±0.53 mg·kg−1·min−1; p〈0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38±0.10 and 0.30±0.18 mg·kg−1·min−1). Therefore, the main defects in subjects with impaired glucose tolerance are decreased first phase insulin secretion and peripheral non-oxidative glucose disposal, but hepatic glucose output shows normal responsiveness to insulin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00401842
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
    Artikel (Nationallizenzen)
    Volltext
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