Liver beta-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes.
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. Bégin-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.
Department of Biochemistry, University of Ottawa, Ontario, Canada.
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Bégin-Heick
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000315:Adrenalectomy; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases