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Ablation of the GNB3 gene in mice does not affect body weight, metabolism or blood pressure, but causes bradycardia. Cell Signal 2014 Nov;26(11):2514-20

Date

08/06/2014

Pubmed ID

25093805

Pubmed Central ID

PMC4160384

DOI

10.1016/j.cellsig.2014.07.030

Scopus ID

2-s2.0-84906069343   13 Citations

Abstract

G protein I?3 (GI?3) is an isoform of heterotrimeric G protein I? subunits involved in transducing G protein coupled receptor (GPCR) signaling. Polymorphisms in GI?3 (GNB3) are associated with many human disorders (e.g. hypertension, diabetes and obesity) but the role of GNB3 in these pathogeneses remains unclear. Here, GI?3-null mice (GNB3(-/-)) were characterized to determine how GI?3 functions to regulate blood pressure, body weight and metabolism. We found GI?3 expression restricted to limited types of tissues, including the retina, several regions of the brain and heart ventricles. GI?3-deficient mice were normal as judged by body weight gain by age or by feeding with high-fat diet (HFD); glucose tolerance and insulin sensitivity; baseline blood pressure and angiotensin II infusion-induced hypertension. During tail-cuff blood pressure measurements, however, GI?3-null mice had slower heart rates (~450 vs ~500 beats/min). This bradycardia was not observed in isolated and perfused GI?3-null mouse hearts. Moreover, mouse hearts isolated from GNB3(-/-) and controls responded equivalently to muscarinic receptor- and I?-adrenergic receptor-stimulated bradycardia and tachycardia, respectively. Since no difference was seen in isolated hearts, GI?3 is unlikely to be involved directly in the GPCR signaling activity that controls heart pacemaker activity. These results demonstrate that although GI?3 appears dispensable in mice for the regulation of blood pressure, body weight and metabolic features associated with obesity and diabetes, GI?3 may regulate heart rate.

Author List

Ye Y, Sun Z, Guo A, Song LS, Grobe JL, Chen S

Author

Justin L. Grobe PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Body Weight
Bradycardia
Diabetes Mellitus
Heterotrimeric GTP-Binding Proteins
Humans
Hypertension
Insulin Resistance
Mice
Mice, Knockout
Obesity
Receptors, G-Protein-Coupled