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  • 1
    ISSN: 1432-0428
    Keywords: Insulin resistance ; glucokinase mutation ; MODY ; glucose clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The chronic hyperglycaemia of glucokinase-deficient diabetes results from a glucose-sensing defect in pancreatic beta cells and abnormal hepatic glucose phosphorylation. We have evaluated the contribution of insulin resistance to this form of chronic hyperglycaemia. Insulin sensitivity, assessed by the homeostasis model assessment (HOMA) method in 35 kindreds with glucokinase mutations, was found to be significantly decreased in 125 glucokinase-deficient subjects as compared to 141 unaffected first-degree relatives. Logistic regression analysis showed that in glucokinase-deficient subjects a decrease in insulin sensitivity was associated with deterioration of the glucose tolerance status. A euglycaemic hyperin-sulinaemic clamp was performed in 14 glucokinase-deficient subjects and 12 unrelated control subjects. In six patients and six control subjects the clamp was coupled to dideutero-glucose infusion to measure glucose turnover. Average glucose infusion rates (GIR) at 1 and 5 mU · kg body weight · min−1 insulin infusion rates were significantly lower in (the glucokinase-deficient) patients than in control subjects. Although heterogeneous results were observed, in 8 out of the 14 patients GIRs throughout the experiment were lower than 1 SD below the mean of the control subjects. Hepatic glucose production at 1 mU · kg body weight−1 · min−1 insulin-infusion rate was significantly higher in patients than in control subjects. In conclusion, insulin resistance correlates with the deterioration of glucose tolerance and contributes to the hyperglycaemia of glucokinase-deficient diabetes. Taken together, our results are most consistent with insulin resistance being considered secondary to the chronic hyperglycaemia and/or hypoinsulinaemia of glucokinase-deficiency. Insulin resistance might also result from interactions between the unbalanced glucose metabolism and susceptibility gene(s) to low insulin sensitivity likely to be present in this population.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Peritoneal ; rat ; glucose kinetics ; closed-loop insulin therapy ; glucose sensor ; bioartificial pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peritoneal glucose kinetics were evaluated in the anaesthetized rat, to assess whether the peritoneal cavity would be a suitable site for the implantation of membrane-protected islets of Langerhans (bioartificial pancreas) or the glucose sensor of an artificial B cell. Glucose was measured in peritoneal fluid samples aspirated by needle puncture. Basal peritoneal and blood glucose concentrations were identical in 16 h fasted (n=4) and non fasted (n=3) animals. After 10 min of an i.v. glucose infusion (n=15) the increment in peritoneal glucose concentration was 63±3% of the increment in blood glucose concentration and both values were significantly correlated (r=0.92; p〈0.001). After 10 min of glucose clamping (12.6±0.8 mmol/l), the increment in peritoneal glucose concentration was 69±3% (n=5; p〈0.05) of the increment in blood glucose concentration. In three additional experiments it was 93±3% of the increment in blood glucose concentration (NS), after 30 min of glucose clamping (8.0±0.5 mmol/l). Peritoneal glucose concentration monitored by a glucose sensor: (a) followed blood glucose sluggishly during a glucose clamp (n=5), confirming the data shown above, (b) followed blood glucose with a 5 min delay and reached the same plateau after the intravenous injection of 1U insulin (n=3; NS). We conclude that peritoneal glucose reflects blood glucose at basal state and during variations of glycaemia, nevertheless, presenting heterogeneous kinetics. These kinetics might be appropriate for a bioartificial pancreas but not for an in vivo calibration procedure, of a peritoneally implanted glucose sensor.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Although clinical and metabolic profiles of families with maturity-onset diabetes of the young (MODY) are diverse5, most MODY patients present a decreased insulin response to glucose, suggesting a primary pancreatic /3-cell defect6. Genes whose products seem to be involved in insulin secretion ...
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The gene encoding the enzyme glucokinase in humans spans a region of 〉20 kilobases (kb) and consists of 12 exons (M.S., J.T., N.V. and G.I.B., manuscript in preparation). The exon-intron organization of the human glucokinase gene is similar to that of the rat4. The regions of the exons were ...
    Type of Medium: Electronic Resource
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