Effect of Glucagon on the Level of Adenosine 3',5'-Monophosphate in Rat Liver and Adipose Tissue: Dependence on the Route of Administration

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Abstract
Studies were conducted on the effect of intraperitoneal (ip) and subcutaneous (sc) injections of glucagon on the levels of cyclic AMP (c-AMP) in the liver and epididymal fat pads of the rat. We observed differences dependent not only on the route of administration of the glucagon but also on the nutritional and hormonal status of the animal. In animals which had been fasted for 18 hr prior to the injection of glucagon, sc injections gave a greater, more prolonged, and less variable elevation of hepatic c-AMP levels than did the ip injections. If animals were fasted overnight, fed for 3 hr and then fasted 3 hr before the injection of glucagon, the ip and sc injection gave equivalent elevations of hepatic c-AMP levels at 10 min. However, the sc injections maintained the elevated levels for the 30 min period studied, whereas the c-AMP in animals receiving ip injections declined rapidly after the peak at 10 min. In contrast to the 2 situations above, the elevation of hepatic c-AMP in adrenalectomized animals was not dependent on the route of administration, since the time course and elevation of c-AMP were nearly equivalent for ip and sc injections. In concurrent measurements of c-AMP levels in epididymal fat pads, under the 3 experimental protocols used, the sc injections always gave a greater elevation of c-AMP in the epididymal fat pads than did the ip injections. This may indicate that ip injections of glucagon are rapidly cleared by the liver, whereas sc injections lead to a greater systemic distribution of the glucagon. Consequently it is apparent that in vivo hormone studies involving c-AMP dependent phenomena must also take into account the route of administration of the hormone in order to observe a maximal response. Induction of tyrosine amino- transferase and increased α-aminoisobutyric acid uptake are discussed in relation to the route of administration of glucagon. (Endocrinology89: 130, 1971)

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