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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Proinsulin ; insulin ; insulin secretion ; insulin resistance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Proinsulin concentrations are increased relative to insulin concentrations in subjects with Type II (non-insulin-dependent) diabetes mellitus. This could be secondary to hyperglycaemia or insulin resistance or due to a defect in insulin secretion. Methods. We investigated the association between fasting insulin, intact proinsulin and the intact proinsulin: insulin ratio with insulin sensitivity, estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and with acute insulin response (AIR) in 182 newly diagnosed Type II diabetic subjects aged 40 to 69 years. None of the subjects was receiving hypoglycaemic medication. Results. Insulin sensitivity correlated inversely with fasting insulin (r s = –0.42) and intact proinsulin (r s = –0.32) (p 〈 0.001). The intact proinsulin:insulin ratio was not correlated with insulin sensitivity. AIR correlated positively with intact proinsulin (r s = 0.23) and inversely with the intact proinsulin:insulin ratio (r s = –0.29, p 〈 0.001). Fasting glucose correlated positively with intact proinsulin (r s = 0.34) and the intact proinsulin:insulin ratio (r s = 0.24, p 〈 0.001). The intact proinsulin:insulin ratio increased by decreasing AIR (quartiles of AIR from high to low: 7.8, 8.2, 9.7 and 12.1 %, p 〈 0.001). This association was independent of age, sex, ethnicity, body mass index, fasting glucose, and insulin sensitivity. Conclusion/interpretation. Insulin resistance (low insulin sensitivity) was not related to the intact proinsulin:insulin ratio in subjects with Type II diabetes. In contrast, both low AIR and high fasting glucose concentrations were associated with a disproportionate increase in proinsulin concentration. These results suggest that increased intact proinsulin:insulin ratio is a marker of a defect in insulin secretion in Type II diabetic subjects. [Diabetologia (1999) 42: 1060–1066]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Insulin resistance ; glycogen synthesis ; non-insulin-dependent diabetes mellitus ; heredity ; candidate gene.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Impaired glycogen synthesis after insulin stimulation accounts for most of the insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM). The glycogen synthase gene (GYS1), which encodes the rate-limiting enzyme for glycogen synthesis, is a promising candidate gene for NIDDM. Therefore, we screened all 16 exons of this gene by single-strand conformation polymorphism analysis in 40 patients with NIDDM (age 67 ± 2 years, body mass index 28.2 ± 0.6 kg/m2) from Taipalsaari, eastern Finland. The Gly464Ser variant (exon 11) and a silent polymorphism TTC342TTT (exon 7) have been reported previously. In addition, we found a new variant Gln71His (exon 2) and a new amino acid polymorphism Met416Val (exon 10). An additional sample of 65 patients with NIDDM and 82 normoglycaemic men (age 54 ± 1 years, body mass index 26.3 ± 1.4 kg/m2) were screened. The allele frequency of the TTC342TTT silent substitution was 0.29 in both NIDDM and normoglycaemic subjects. The Gln71His and Gly464Ser variants were found in 1 (1 %) and 3 (3 %) subjects, respectively, of the 105 NIDDM patients and in none of the 82 normoglycaemic men. The Met416Val polymorphism was found in 16 (15 %) of the 105 NIDDM patients and in 14 (17 %) of the 82 control subjects (all heterozygous). The Met416Val polymorphism was not associated with insulin resistance in two groups of normoglycaemic subjects. In conclusion, the new Gln71His and Met416Val substitutions and other variants of the glycogen synthase gene are unlikely to make a major contribution to insulin resistance and NIDDM in diabetic patients from eastern Finland. [Diabetologia (1997) 40: 1313–1319]
    Type of Medium: Electronic Resource
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