2011
DOI: 10.1007/s00125-011-2062-3
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The effect of antecedent hypoglycaemia on β2-adrenergic sensitivity in healthy participants with the Arg16Gly polymorphism of the β2-adrenergic receptor

Abstract: Aims/hypothesisHomozygosity for glycine at codon 16 (GlyGly) of the β2-adrenergic receptor may alter receptor sensitivity upon chronic stimulation and has been implicated in the pathogenesis of hypoglycaemia unawareness. We compared the effect of antecedent hypoglycaemia on β2-adrenergic receptor sensitivity between GlyGly participants and those with arginine 16 homozygosity (ArgArg) for the β2-adrenergic receptor.MethodsWe enrolled 16 healthy participants, who were either GlyGly (n = 8) or ArgArg (n = 8). The… Show more

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Cited by 6 publications
(3 citation statements)
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“…These observations are consistent with previous studies suggesting that administration of the B2AR agonist terbutaline may restore hypoglycemia awareness and reduce nocturnal hypoglycemia ( 22 , 23 ). This effect may be particularly useful in humans with homozygosity for glycine at codon 16 (GlyGly) of the B2AR who appear to show reduced B2AR sensitivity to antecedent hypoglycemia ( 24 ). Moreover, the current data are consistent with recent data indicating that repeated adrenergic receptor activation might also be involved in the generation of hypoglycemia-associated autonomic failure ( 25 ) and raise the possibility that B2AR receptor downregulation might play a role in this phenomenon.…”
Section: Discussionmentioning
confidence: 99%
“…These observations are consistent with previous studies suggesting that administration of the B2AR agonist terbutaline may restore hypoglycemia awareness and reduce nocturnal hypoglycemia ( 22 , 23 ). This effect may be particularly useful in humans with homozygosity for glycine at codon 16 (GlyGly) of the B2AR who appear to show reduced B2AR sensitivity to antecedent hypoglycemia ( 24 ). Moreover, the current data are consistent with recent data indicating that repeated adrenergic receptor activation might also be involved in the generation of hypoglycemia-associated autonomic failure ( 25 ) and raise the possibility that B2AR receptor downregulation might play a role in this phenomenon.…”
Section: Discussionmentioning
confidence: 99%
“…However, differences in phenotype may also be a result of differences in sensitivity to β-agonists, as the Arg 16 allele is associated with enhanced agonist-mediated desensitization (Dishy et al, 2001 ) and attenuated blood flow during infusion of a β-agonist in the brachial artery (Garovic et al, 2002 ). In contrast, Arg 16 homozygotes had increased β 2 -receptor sensitivity after hypoglycemia whereas no effect was seen in Gly 16 homozygotes (Schouwenberg et al, 2011 ). Also, the G16R polymorphism has been associated with insulin resistance (Masuo et al, 2005 ) and obesity (Daghestani et al, 2012 ), albeit with inconsistent results (Gjesing et al, 2009 ).…”
Section: Introductionmentioning
confidence: 99%
“…This finding has been reproduced in six studies in five different populations by four independent research groups (10, 11, 12, 13, 14, 15). Schouwenberg and coworkers showed in healthy adults that possessing the Arg Arg (vs the Gly Gly) polymorphism of the β2-adrenergic receptor may to some extent protect against the development of hypoglycaemia unawareness (16, 17), a major risk indicator of severe hypoglycaemia. In contrary Holstein et al .…”
Section: Introductionmentioning
confidence: 99%