Adrenalectomy-induced alterations in glucagon binding and lipolysis in isolated rat adipocytes.
Adipocytes from adrenalectomized rats nearly lost their lipolytic response to glucagon concomitant with a 90% decrease in the number of glucagon receptors per cell. Quantitative analysis of the relation between amount of cell-bound glucagon and hormone-stimulated lipolysis revealed that the ability of the remaining 10% of glucagon receptors to induce lipolysis was not impaired. Binding of the beta-adrenergic antagonist [3H]dihydroalprenolol and maximal lipolysis induced by (-)-isoproterenol, (Bu)2cAMP, 3-isobutyl-1-methylxanthine, and adenosine deaminase were reduced only 10 to 20% after adrenalectomy. Furthermore, glucagon-stimulated cAMP production was greatly decreased in adrenalectomized animals, but isoproterenol-stimulated cAMP production was not. Hydrocortisone replacement in adrenalectomized rats only partially prevented the loss of glucagon receptors and glucagon effects on both cAMP production and lipolysis. These findings suggest that lipolytic cascade distal to hormone receptors was not greatly impaired in adipocytes after adrenalectomy and that the unresponsiveness of these cells to glucagon was mostly due to a marked reduction in the number of glucagon receptors.
Division of Endocrinology and Metabolism, Asahi Life Foundation, Toho University School of Medicine, Tokyo, Japan.
K
K
Watanabe
M
M
Irie
H
H
Kajinuma
K
K
Suzuki
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism*; D000315:Adrenalectomy; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004082:Dihydroalprenolol / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D018027:Receptors, Glucagon
D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D004082:Dihydroalprenolol; D003994:Bucladesine; D005934:Glucagon; D000242:Cyclic AMP; D000243:Adenosine Deaminase; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine