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  • 1
    ISSN: 1432-5233
    Keywords: Key words Non-insulin-dependent diabetes mellitus ; MODY ; Hepatocyte nuclear factor-1α ; Genetics ; Microsatellite polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, hepatocyte nuclear factor-1α (HNF-1α, which is encoded by the TCF1 gene) mutations were reported in a subset of patients with maturity onset diabetes of the young (MODY3). We studied the contribution of TCF1 to genetic susceptibility to common non-insulin-dependent diabetes mellitus (type 2) in Japanese subjects by investigating allelic association with type 2 diabetes use of three markers. We also studied the frequency of the G191D mutation, the only mutation of TCF1 reported so far in late-onset type 2 diabetes. A total of 356 subjects were studied. There were no significant differences in allele frequency of the three markers between patients with type 2 diabetes and control subjects. A G191D mutation was not found in the subjects studied, giving a frequency of less than 0.4% in common type 2 diabetes. The lack of association of type 2 diabetes with three markers in and near TCF1 suggests that mutations in TCF1 derived from a limited number of founders are not a major cause of common type 2 diabetes even in the genetically homogeneous Japanese population. The data also indicate that the G191D mutation in TCF1 plays little, if any, role in susceptibility to common type 2 diabetes in the Japanese.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Adenosine ; Phenylisopropyladenosine ; Adenosine receptors ; Negative inotropic effect ; G proteins ; Ferret ventricular myocardium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An adenosine A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA) elicited a pronounced negative inotropic effect with the EC50 value of 0.69 μmol/1 in the presence of a β-adrenoceptor blocking agent bupranolol (0.3 μmol/1) in the isolated ferret papillary muscle. The negative inotropic effect of R-PIA was not associated with changes in cyclic AMP level. Adenosine and other A1 receptor agonists also elicited a negative inotropic effect. DPCPX (1,3-dipropyl-8-cyclopentyl xanthine) antagonized the negative inotropic effect of R-PIA in a competitive manner (pA2 value = 8.4). The inhibitory action of R-PIA was markedly attenuated in the ventricular muscle preparation isolated from ferrets pretreated with pertussis toxin that caused ADP-ribosylation of 39 kDa proteins in the membrane fraction. In the membrane fraction derived from the ferret ventricle, [3H]-DPCPX bound to a single binding site in a saturable and reversible manner with high affinity (Kd value = 1.21±0.41 nmol/l; B max = 12.8±3.02 fmol/mg protein; n = 7). The binding characteristics of [3H]-DPCPX in the rat ventricle (Kd value = 1.51 ±0.09 nmol/l; B max = 12.7±1.47 fmol/mg protein; n = 5) were similar to those in the ferret. On the other hand, the content of Go, a major pertussis toxin-sensitive G protein in the ferret heart, was much higher in the ferret than in the rat ventricle. The present results indicate that adenosine receptors may play an important role in the inhibitory regulation of ventricular contractility in the ferret in contrast to other mammalian species. The signal transduction process subsequent to agonist binding to A1 receptors including the pertussis toxin-sensitive G protein and ion channels may be responsible for the unique inhibitory action of adenosine in this species.
    Type of Medium: Electronic Resource
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