Effect of Glucagon on the Metabolism of Lipids and on Urea Formation by the Perfused Rat Liver

Abstract

Livers obtained from fed or fasted rats were perfused with blood from fasted rats with and without the addition of glucagon and/or a hyperlipemic serum (HLS).In addition to its well-known hyperglycemic effect, glucagon increased the blood levels of the ketone bodies and of urea, and decreased the levels of cholesterol, total lipids and NEFA.The magnitude of the effects noted were dependent upon the previous state of the liver and the addition of the hyperlipemic serum.In the fed liver, glucagon produced a greater degree of hyperglycemia than in the fasted liver and this effect was enhanced by the addition of a hyperlipemic serum. In fasted livers the addition of a hyperlipemic serum did not increase the hyperglycemia produced by glucagon alone.Total lipids, cholesterol and NEFA were decreased when glucagon was added to either the fasted or fed liver, in the presence or absence of a hyperlipemic serum.Glucagon caused a greater increase in the level of ketone bodies in the fasted than in the fed liver and this effect was increased by the addition of a serum rich in lipids.The addition of glucagon caused an increase in the levels of urea and this effect was reduced when a hyperlipemic scrum was acMted. DIABETES 15:74048, October, 1966. A survey of the available literature on the effects of glucagon on various aspects of lipid metabolism discloses unexplained discrepancies in the results. On the one hand it has been reported that glucagon is lipolytic and in the main inhibits the synthesis of fat and cholesterol. 5 ' 21 ' 22 ' 36 ' 43 ' 52 On the other hand there also exist data to show that glucagon lowers the concentration of fatty acids in the plasma and increases fat synthesis. 1 -14 ' 43 In the case of ketone body metabolism,

A Versatile Method for the <i>in vitro</i> Perfusion of Isolated Organs of Rats and Mice with Particular Reference to Liver

“…Similar findings were observed by other authors [7,8,34, 35j although Fisher [15] did not observe any change in liver glycogen.…”

Interactions of Glucagon and Insulin on the Metabolism of Perfused Livers from Fasted Rats

“…A direct protein catabolic effect of glucagon is well-documented [7, 18--20,221. At least part of the carbon arising from endogenous liver protein can be accounted for by increased glucose formation which is observed in the absence of gluconeogenic substrate following glucagon addition [6,9,18,19,20]. That glucagon has an additional catabolic effect on liver fat metabolism is supported by several lines of evidence.…”

Effects of Catecholamines on Metabolism

“…Glucagon, dBcAMP and theophylline increase the concentration of acetyl CoA and acyl CoA and decrease the concentration of free CoA in liver slices (CLAYCOMB and KILSHEIMER, 1969). Glucagon and dBcAMP also increase ketogenesis (BEWSHER and ASHMORE, 1966;HEIMBERG et al, 1969;MENAHAN and WIELAND, 1967;STRUCK et al, 1965;VAN HARKEN et al, 1969;PENHOS et al, 1966;REGEN and TERRELL, 1968) as well as gluconeogenesis (see previous section). This similarity between the effects of glucagon and cAMP on the one hand and of FF A on the other has led to the hypothesis that the gluconeogenic and ketogenic actions of glucagon and of cAMP that mediate these effects are secondary to a rise in intracellular FFA concentration brought about by stimulation of a hepatic triglyceride lipase.…”