J. Lipid Res.
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Journal of Lipid Research, Vol. 15, 26-32, January 1974
Copyright © 1974 by Lipid Research, Inc.

Studies of glucagon resistance in large rat adipocytes: 125I-labeled glucagon binding and lipolytic capacity

James N. Livingston , Pedro Cuatrecasas , and Dean H. Lockwood

Departments of Medicine and Pharmacology and Experimental Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

This study is concerned with potential modifications of large fat cells from adult rats (400-450 g) that make them resistant to stimulation by glucagon. The lipolytic capacity and 125I-labeled glucagon-binding capability of these cells were compared with these properties of small glucagon-sensitive cells from young rats (130-160 g). As determined by maximal stimulation with theophylline, dibutyryl cAMP, or epinephrine, the lipolytic capacity of large cells was not markedly different from small cells, which suggests that an alteration contributing to glucagon insensitivity is not present in the enzymes involved with hormone-mediated lipolysis. Glucagon-binding studies did indicate a difference between the two cell types. Both large cells and particulate fractions from large cells bound less 125I-labeled glucagon than small cells or small-cell particles. That diminished binding is not a consequence of glucagon degradation is indicated by the similar amounts of 125I-labeled glucagon degraded by both cell types. The decrease in 125I-labeled glucagon binding was not as marked as the decrease in lipolytic response to glucagon stimulation. This lack of correlation and the relationship between elevated phosphodiesterase levels and glucagon insensitivity described in the accompanying report suggest that diminished binding explains only in part the marked resistance to glucagon found in large cells.

Supplementary key words isolated fat cells • hormone-stimulated lipolysis • phosphodiesterase • resistance to glucagon • 125I-labeled glucagon binding • glucagon degradation

Submitted on February 20, 1973
Revised on May 24, 1973
Accepted on August 28, 1973


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