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Publication : Liver beta-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes.

First Author  Bégin-Heick N Year  1994
Journal  Am J Physiol Volume  266
Issue  6 Pt 1 Pages  C1664-72
PubMed ID  8023896 Mgi Jnum  J:18963
Mgi Id  MGI:67195 Doi  10.1152/ajpcell.1994.266.6.C1664
Citation  Begin-Heick N (1994) Liver beta-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes. Am J Physiol 266(6 Pt 1):C1664-72
abstractText  The ob and db genes produce similar hormonal anomalies in mice. Although the expression of the syndromes diverges with age, at 8-12 wk both ob/ob and db/db mice are hyperglycemic and hyperinsulinemic and show evidence of hypercorticoidism. Nevertheless, membranes isolated from livers of ob/ob and db/db mice behave differently in terms of adenylyl cyclase activity and beta-adrenergic receptor function. There are three times as many beta 2-adrenergic receptor binding sites and a threefold increase in the response to catecholamines in ob/ob mouse liver membranes than in comparable preparations from normal controls or db/db mice. By contrast, the two main G proteins of liver membranes (Gs alpha and Gi alpha 2) are less abundant in the mutants, ob/ob and db/db, than in their respective lean controls. Adrenalectomy normalizes the exaggerated response to beta-adrenergic agonists and the number of beta-adrenergic binding sites in the ob/ob mouse. This shows that the enhanced beta-adrenergic receptor response is linked to hypercorticoidism. Cellular maturation and differentiation (D. C. Watkins, J. K. Northrup, and C. C. Malbon, J. Biol. Chem. 262: 10651-10657, 1987) and diseases such as obesity and diabetes (cf. N. McFarlane-Anderson, J. Bailly, and N. Begin-Heick, Biochem. J. 282: 15-23, 1992) have been associated with modifications in the complement of G proteins detected in cells. However, the relationship among levels, types, and intracellular localization of G proteins in tissues and their influence on the transduction of the message to an effector system, such as adenylyl cyclase, are not yet well understood.
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