Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes

Obesity ◽  
2013 ◽  
Vol 21 (8) ◽  
pp. 1720-1725 ◽  
Author(s):  
Ewa-Carin Långberg ◽  
Mohammed Seed Ahmed ◽  
Suad Efendic ◽  
Harvest F. Gu ◽  
Claes-Göran Östenson
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Association ◽  
Adrenergic Receptor ◽  
Receptor Alpha

Estrogen receptor alpha gene variants associate with type 2 diabetes and fasting plasma glucose

2008 ◽  
Vol 18 (11) ◽  
pp. 967-975 ◽  
Author(s):  
Ingrid Dahlman ◽  
Martine Vaxillaire ◽  
Maria Nilsson ◽  
Cecile Lecoeur ◽  
Harvest F. Gu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Estrogen Receptor ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Estrogen Receptor Alpha ◽  
Gene Variants ◽  
Receptor Alpha ◽  
Estrogen Receptor Alpha Gene ◽  
Alpha Gene

Abstract 13045: Chronic Beta3-Adrenergic Receptor Antagonist Therapy Rescues Diabetic Cardiomyopathy in a Mouse Model With Type 2 Diabetes: Insights into Cellular Mechanism

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jing Cao ◽  
Xiaoqiang Sun ◽  
Heng Jie Cheng ◽  
Yixi Liu ◽  
Dalane Kitzman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Diabetic Cardiomyopathy ◽  
Adrenergic Receptor ◽  
Effective Prevention ◽  
Glucose Levels ◽  
Wild Type Female ◽  
Myocyte Function ◽  
Myocyte Contractility

Background: Diabetic cardiomyopathy (DCM) leads to progressive decline in cardiac function, increasing the risk for heart failure. There are no known effective prevention approaches or therapeutic strategies. Recent evidence in diabetes mellitus (DM) human and animal hearts suggests that the up-regulation of β 3 -adrenergic receptor (AR)-mediated inhibitory pathway may be responsible for the progression of DCM. However, its precise role is still being debated. We hypothesize that β 3 -AR antagonists (β 3 -ANT) may rescue the detrimental effects of β 3 -AR activation, improve cardiomyocyte function, and preserve normal β-AR regulation, leading to the regression of DCM. Methods: We compared LV myocyte function, [Ca 2+ ] i transient ([Ca 2+ ] iT ) at baseline and responses to β-AR simulation with isoproterenol (ISO,10 -8 M) in 3 groups wild-type female mice over 14 weeks (W):1) Type 2 DM ( T2 ) (n=9), 14 W fed high-fat diet (HFD), but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days); 2) T2/β 3 -ANT (n=7), T2 mice at 10 W received L-748,337, a selective β 3 -ANT (10 -7 M/kg/day, mini-pump) for 4 W; and 3) Vehicle controls (C) (n=9). Results: Versus C, T2DM was induced in mice received HFD and low dose STZ with significantly elevated blood glucose levels (T2: 388, T2/β 3 -ANT: 369 vs C: 128 mg/dl). In T2, LV myocyte basal function and [Ca 2+ ] iT regulation were impaired measured as significantly decreased myocyte contractility (dL/dt max ) (76.8 vs 135.2 μm/s), relengthening (dR/dt max ) (62.1 vs 113.8 μ m/s) and [Ca 2+ ] iT (0.16 vs 0.21). Furthermore, versus C, in T2 myocytes, ISO-induced increases in dL/dt max (T2: 40% vs C: 58%), dR/dt max (35% vs 54%) and [Ca 2+ ] iT (19% vs 30%) were significantly reduced. By contrary, versus T2, T2/β 3 -ANT myocytes showed normal basal cell contraction (127.8 μm/s), relaxation (109.4 μm/s) and [Ca 2+ ] iT (0.21) with preserved ISO-stimulated positive inotropic effect. Versus C, in T2/β 3 -ANT, ISO caused similar increases in dL/dt max (57%), dR/dt max (52%) and [Ca 2+ ] iT (30%). Conclusion: Chronic β 3 -ANT leads to the preservation of LV myocyte function, [Ca 2+ ] iT , and β-AR responsiveness in a mouse model of type 2 diabetes. Thus, antagonizing β 3 -AR might provide a new therapeutic strategy for DM-related decline in myocardial function.

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