Regulation of peripheral lipogenesis by glucagon. Inability of the hormone to inhibit lipogenesis in rat mammary acini in vitro in the presence or absence of agents which alter its effects on adipocytes.

摘要

The rate of lipogenesis in acini isolated from mammary glands of mid-lactating rats was studied by measuring the rate of incorporation of 3H from 3H2O into total lipid and fatty acids, with glucose as substrate. Glucagon did not affect the rate of lipogenesis in acini. Glucagon did not antagonize the maximal stimulatory effect of insulin, nor did it alter the insulin dose-response curve. Theophylline, at concentrations up to 20 mM, was a potent inhibitor of lipogenesis in acini. Glucagon did not augment the degree of inhibition of lipogenesis induced by 5 mM-theophylline. The results suggest that mammary-gland acini do not respond to glucagon in vitro under conditions in which the hormone induces inhibition of lipogenesis (the present paper) and of individual key steps in the lipogenic pathway in adipocytes [Zammit & Corstorphine (1982) Biochem. J. 208, 783-788; Green (1983) Biochem. J. 212, 189-195]. In agreement with these observations, we could detect only a minimal degree of specific binding of 125I-labelled glucagon to acini which bound insulin normally. This difference in responsiveness of mammary and adipose cell preparations in vitro to glucagon suggests that the two tissues may be differentially responsive to changes in the circulating insulin/glucagon concentration ratio in vivo. The significance of these findings for the regulation of substrate utilization for lipogenesis in the two tissues during lactation is discussed.