The Arg16Gly polymorphism of human β2‐adrenoreceptor is associated with type 2 diabetes in Taiwanese people

Chang, Tien-Jyun; Tsai, Ming‐Han; Yin, Jiuli; Lee, Bor-Heng; Lee, Kuan-Ching; JinYu, Lin; Chiu, Ken C.; Tai, Tong-Yuan; Chuang, Lee‐Ming

doi:10.1046/j.1365-2265.2002.01661.x

Cited by 26 publications

(21 citation statements)

References 30 publications

(41 reference statements)

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“…Noteworthy, Arg16/Gln27 patients were on average 10 y younger, more often had an ischemic cause of their cardiomyopathy, and more often had hypertension and diabetes mellitus. Apart from the difference in age, these observations are in line with previous studies (12,32,33). The reason for the difference in age is unclear, since the Arg16/Gln27 haplotype does not influence survival in patients with HF (34) and seems not to be a risk factor for HF (35).…”

Section: Discussionsupporting

confidence: 80%

Differential Effects of Nonselective Versus Selective β-Blockers on Cardiac Sympathetic Activity and Hemostasis in Patients with Heart Failure

et al. 2013

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Carvedilol, a nonselective b-blocker, may be more effective than the selective b-blocker metoprolol in reducing the risk of thromboembolic events in heart failure. The aim of this study was, first, to assess whether there is a differential response in cardiac sympathetic activity by 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) imaging when either b-blocker is used. Second, we assessed whether that response correlates with levels of various serum factors that serve as markers for coagulability. Methods: In this prospective, randomized, open-label crossover study with masked outcome assessments, stable heart failure patients (left ventricular ejection fraction , 40%) homozygous for the Arg16/Gln27 (n 5 13) or Gly16/Glu27 haplotype (n 5 8) of the b 2 -receptor were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk periods. Primary outcome was sympathetic activity as measured by 123 I-MIBG myocardial washout. Secondary outcomes included markers of hemostasis. Results: 123 I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment (12.9% 6 3.9% vs. 22.1% 6 2.8%, respectively, P 5 0.003), irrespective of b 2 -adrenergic receptor haplotype. In addition, treatment with carvedilol resulted in a lower von Willebrand factor than did metoprolol (149% 6 13% vs. 157% 6 13%, respectively, P 5 0.01), irrespective of b 2 -adrenergic receptor haplotype. Conclusion: Compared with metoprolol, carvedilol resulted in greater reduction of sympathetic activity after 6 wk of treatment and lower von Willebrand factor concentrations in both Arg16/ Gln27 and Gly16/Glu27 individuals. Therefore, carvedilol may reduce the risk of thromboembolic events in patients with heart failure, irrespective of b 2 -receptor haplotype status.

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Section: Discussionsupporting

confidence: 80%

Differential Effects of Nonselective Versus Selective β-Blockers on Cardiac Sympathetic Activity and Hemostasis in Patients with Heart Failure

et al. 2013

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“…The age is believed to be one of the strongest risk factors for the T2DM [18]. Also UCP3 and ADRB2 were both previously shown to be involved in T2DM by biological and medical studies [7,15]. In particular, the ADRB2-16 variant seems to alter the extent of the agonist-induced lipolysis magnitude [36] and to down regulate the receptor expression [35].…”

Section: Discussionmentioning

confidence: 99%

β2-adrenergic receptor and UCP3 variants modulate the relationship between age and type 2 diabetes mellitus

Pinelli¹,

Giacchetti²,

Acquaviva³

et al. 2006

BMC Med Genet

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Background: It is widely accepted that Type 2 Diabetes Mellitus (T2DM) and other complex diseases are the product of complex interplay between genetic susceptibility and environmental causes. To cope with such a complexity, all the statistical and conceptual strategies available should be used. The working hypothesis of this study was that two wellknown T2DM risk factors could have diverse effect in individuals carrying different genotypes. In particular, our effort was to investigate if a well-defined group of genes, involved in peripheral energy expenditure, could modify the impact of two environmental factors like age and obesity on the risk to develop diabetes. To achieve this aim we exploited a multianalytical approach also using dimensionality reduction strategy and conservative significance correction strategies.

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“…One mutation known to decrease receptor density and efficiency is Arg16Gly, which is associated with longitudinal increases in weight gain in a large cohort of male children [32]. In other studies, the same mutation has been associated with a greater relative risk for developing Type 2 diabetes [33]. The alteration in fatty acid metabolism associated with polymorphisms of the β2-adrenergic receptor makes this gene a possible "thrifty gene" candidate.…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes

Anis¹,

Leshem²,

Reuveni³

et al. 2004

Diabetologia

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Aims/hypothesis. G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes. Methods. Synthetic peptides derived from a kinasesubstrate interaction site in GRK2/3 were initially screened for their effect on in vitro melanogenesis, a GRK-mediated process. The most effective peptides were administered intraperitoneally, utilising a variety of dosing regimens, to Psammomys obesus gerbils, Zucker diabetic fatty (ZDF) rats, or db/db mice. The metabolic effects of these peptides were assessed by measuring fasting and fed blood glucose levels and glucose tolerance. Results. Two peptides, KRX-683 107 and KRX-683 124 , significantly reduced fed-state blood glucose levels in the diabetic Psammomys obesus. In animals treated with KRX-683 124 at a dose of 12.5 mg/kg weekly for 7 weeks, ten of eleven treated animals responded with mean blood glucose significantly lower than controls (4.7±0.4 vs 16.8±0.8 mmol/l, p≤0.0001). Significant reductions in blood glucose compared with controls were also seen in ZDF rats administered KRX-683 124 and in db/db mice, which had significantly reduced fasting and 2-hour postprandial glucose levels after the treatment. Conclusions/interpretation. Sequence-based peptides derived from GRK2/3 have an antidiabetic effect demonstrated in three different animal models of Type 2 diabetes. By modulating GRK2/3 activity, these peptides enhance GPCR-initiated signal transduction, resulting in improved glucose homeostasis. Sequencebased peptide modulation of GRK could prove useful in the treatment of Type 2 diabetes.

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The Arg16Gly polymorphism of human β2‐adrenoreceptor is associated with type 2 diabetes in Taiwanese people

Cited by 26 publications

References 30 publications

Differential Effects of Nonselective Versus Selective β-Blockers on Cardiac Sympathetic Activity and Hemostasis in Patients with Heart Failure

Differential Effects of Nonselective Versus Selective β-Blockers on Cardiac Sympathetic Activity and Hemostasis in Patients with Heart Failure

β2-adrenergic receptor and UCP3 variants modulate the relationship between age and type 2 diabetes mellitus

Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes

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