Decreased glucagon binding and glucagon-stimulated lipolysis in adipocytes from streptozotocin-diabetic rats.
Adipocytes from streptozotocin-diabetic rats showed a markedly reduced lipolytic response to glucagon concomitant with a 90% or greater decrease in the number of glucagon receptors per cell. In contrast, beta-adrenergic receptors assessed by [3H]dihydroalprenolol binding and lipolysis stimulated by isoproterenol, dibutyryl 3'5'-cyclic AMP and 3-isobutyl-1-methylxanthine were reduced by only 10-25% in diabetic rats compared with controls. Furthermore, quantitative analysis of the relationship between the amount of cell-bound glucagon and the hormone-stimulated lipolysis revealed that the function of the remaining 10% of glucagon receptors remained intact in cells from diabetic animals. These findings suggest that the lipolytic cascades, including beta-adrenergic receptors, in adipocytes are not greatly impaired by diabetes, and therefore, the unresponsiveness of these cells to glucagon is mostly due to a marked reduction in the number of glucagon receptors, probably as a result of a down-regulation by postprandial hyperglucagonemia.
Sato
N
N
Division of Endocrinology and Metabolism, Asahi Life Foundation, Tokyo, Japan.
Irie
M
M
Kajinuma
H
H
Suzuki
K
K
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D005934:Glucagon / Q000008:administration & dosage*; D007545:Isoproterenol / Q000008:administration & dosage; 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; D005934:Glucagon; D007545:Isoproterenol