Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Steven T. Russell, Michael J. Tisdale

Research output: Contribution to journalArticle

Abstract

Objectives: The goal of the current study is to determine whether the ß-adrenoreceptor (ß-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-a2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human ß1-, ß2-, ß3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the ß3-AR with higher affinity (Kd 46±1nM) than the ß2-AR (Kd 71±3nM) while there was no binding to the ß1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various ß-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of ß3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of ß1- and ß2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific ß-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a ß-3AR, or possibly a ß2-AR.
Original languageEnglish
Pages (from-to)590-599
Number of pages10
JournalBBA - Molecular and Cell Biology of Lipids
Volume1821
Issue number4
Early online date23 Dec 2011
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Adrenergic Receptors
Zinc
Glycoproteins
Obesity
Glucose
CHO Cells
Propranolol
Cyclic AMP
Skeletal Muscle
Body Weight
Insulin
White Adipose Tissue
Brown Adipose Tissue
Glucose Tolerance Test
Body Temperature
Insulin Resistance
Adipose Tissue
Muscles
Proteins
Amberlite XAD-2 resin

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. >. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Russell, ST & Tisdale, MJ, 'Role of ß-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-a2-glycoprotien (ZAG)', BBA - molecular and cell biology of lipids , vol 1821, no. 4 (2012) DOI http://dx.doi.org/10.1016/j.bbalip.2011.12.003

Keywords

  • zinc-α2-glycoprotein
  • β-adrenoreceptor
  • obesity
  • diabetes

Cite this

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abstract = "Objectives: The goal of the current study is to determine whether the {\ss}-adrenoreceptor ({\ss}-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-a2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human {\ss}1-, {\ss}2-, {\ss}3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the {\ss}3-AR with higher affinity (Kd 46±1nM) than the {\ss}2-AR (Kd 71±3nM) while there was no binding to the {\ss}1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various {\ss}-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of {\ss}3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of {\ss}1- and {\ss}2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific {\ss}-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a {\ss}-3AR, or possibly a {\ss}2-AR.",
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Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG). / Russell, Steven T.; Tisdale, Michael J.

In: BBA - Molecular and Cell Biology of Lipids , Vol. 1821, No. 4, 04.2012, p. 590-599.

Research output: Contribution to journalArticle

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AU - Russell, Steven T.

AU - Tisdale, Michael J.

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