Induction of Sensitivity to the Insulin-Like Action of Growth Hormone in Normal Rat Adipose Tissue*

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Abstract
The initial exposure of adipose tissue from hypophysectomized rats to GH results in an insulin-like response, characterized by increased utilization of glucose, pyruvate, and leucine and antilipolysis. These effects disappear after 2 or 3 h and are followed by a period of refractoriness in which reexposure of the tissues to GH fails to elicit an insulin-like response. Adipose tissue from normal rats is refractory to the insulin-like effects of GH when tested in the initial hour after excision, but incubation of such tissues without GH for 2 h or more restores sensitivity to the insulin-like action of GH added in the third, fourth, or fifth hour after excision. One microgram of GH per ml added in the fourth hour produced effects equivalent to approximately 50 μU/ml insulin. Increases in the oxidation of glucose, pyruvate, and leucine and in the incorporation of glucose carbons into fatty acids were seen, along with inhibition of epinephrineinduced lipolysis. These effects could be initiated with aslittle as 100–300ng/ml ovine GH. Refractoriness was sustained through the prolonged incubation period when 300 ng/ml, a physiological concentration of GH, were added for only the first 15 min of incubation or for the entire 3-h preincubation period. Loss of refractoriness was also prevented by adding 20 μg/ml of cycloheximide to the initial incubation medium, suggesting that the ability to regain a response to GH in an insulin-like fashion might require protein synthesis. In contrast, 5 μg/ml actinomycin did not prevent the appearance of the insulin-like response, suggesting that RNA synthesis was not involved. These observations indicate that GH can produce or sustain refractoriness in tissues that cannot respond to the insulin-like effect of GH and suggest that the burst of GH secretion observed every 3 or 4 h in rats may be responsible, and perhaps physiologically necessary, for maintaining tissues in a refractory state.