The physiological effect of glucagon on fat-mobilisation

Abstract

Summary. In normal dogs under pentobarbital anaesthesia, intraportal infusion of physiological doses (0.002 /~g/kg/min) of cystein-treated glucagon increases markedly the plasma FFA levels in the peripheral blood. This can be considered as an argument for a possible role of glucagon as a physiological regulator of lipid metabolism. Effet physiologique du glucagon sur la mobilisation des lipides.Rgsumd. La perfusion portMe de doses physiologiques (0.002 #g/kg/min) de glucagon trait6 par la cystdine augmente de fagon trbs signifieative le taux sanguin des aeides gras libres du plasma pgriphdrique. Cette observation constitue un argument en faveur d'un r61e physiologique du glucagon dans le m6tabolisme des lipides.Der physiologischc Effe/ct yon Glucagon auf die ~ett-mobilisation.Zusammenfassung. Die intraportale Infusion von physiologisehen Dosen von Glucagon, das mit Cystein behandelt ist (0.002 #g/kg/min) erhSht bei normalen Hunden unter Pentobarbital-Anaesthesie eindeutig die Plasmaspiegel der freien Fetts~uren im peripheren Blur. Dieset Effekt kann als Hinweis auf die physiologische Bedeutung des Glucagons im Fettstoffwechsel angesehen werden.In vitro, glucagon increases free fatty acid release from rat adipose tissue (STEINBEI~G et al., 1959; HA-GEN, 1960;WEINGES, 1961). This effect results from increased lipolysis (WEINOES and L6F]~L]~R, 1965) with concomitant increased re~sterification as shown by VAVGHAN and STEI~BEaG (1963) with their "non isotopic balance method", and by ourselves (LEFEBV~E, 1966).An effect on FFA release has been detected by WEING]SS (1961) with concentrations of glucagon of 0.004 #g/ml and by LV.FEBV~E (1966) with concentrations of 0.002/~g/ml, which are in the range of the physiological levels evaluated in plasma by U~GER et al. (1962).In vivo, the effects of glucagon on plasma FFA have led to conflicting results: a fall in plasma FFA in man was observed by LrSSETT et al. (1960), PENNICK and tIINKLE (1960), EY~ER et al. (1961 and D~EmI~G et al. (1962), andin dog by STEr~BERG et al. (1959); an early rise by WEIZCGES (1961) in man, and by LEVARLET (1962) in dog; an initial fall and a secondary rise, in man, byFELBER and van ITALLIE (1958) and by LIPSETT et al. (1960). We recently reported (LE]~V~BV~E, 1965) that, in man, glucagon at the dose of 1 mg/m ~, induces an initial fall of plasma FFA followed by a marked secondary rise, which can be observed between the 2nd and 5th hour after the injection. This initial fall can be reproduced by an hyperglycemia of the same magnitude as the one caused by glueagon, and induced by i. v. glucose infusion. The secondary rise is much more important after glucagon than the small rebound-effect observed after glucose. This secondary rise could correspond to the fat-mobilizing effect of the hormone.Nevertheless the physiological signification of these experiments has not been established. In the experiments reported here, we studied the effects on plasma FFA of physiological doses of glucagon perfused in the physiological site of secretion of the ho...

The Effects of Glucagon on Plasma Concentrations of Insulin. Growth Hormone, Glucose and Free Fatty Acids in Sheep: Comparison with the Effects of Catecholamines

“…The decrease in the plasma FF A level of sheep during glucagon infusion is also consistent with the findings in man (Crockford et al 1966) and indicates either that glucagon has little lipolytic activity in sheep or that any lipolytic action of glucagon [comparable to that observed in dogs (Lefebvre 1966) or during in vitro studies on rat adipose tissue (Hagen 1961)] is obscured by the antilipolytic effect of the insulin secreted during glucagon infusion. The initial increase in FF A during infusion of glucagon may indicate a lipolytic effect of the hormone obscured later by the antilipolytic effect of insulin; a similar biphasic effect has been observed in dogs after glucagon injection (Whitty et al 1969).…”

Glucagon levels and metabolic effects in fasting man

“…(29) and in vivo in other species (30) was not evident in these studies, in that plasma-free fatty acid and blood glycerol concentrations did not rise significantly.…”

Substrate Turnover during Prolonged Exercise in Man

“…Although the in vivo evidence for a gluconeogenic effect of glucagon in intact man is less compelling (33), it is possible that the rise in arterial glucagon contributed to the augmented uptake of glucose precursors in the present study, an effect which would be enhanced by the simultaneous fall in arterial insulin (34). These hormonal changes may also have favored hepatic gluconeogenesis by stimulating adipose tissue lipolysis (35,36), thereby making increased quantities of glycerol and FFA available to the liver. It should be enmphasized, however, that exercise-induced changes in gluconeogenesis may reflect the cumulative effect of increased secretion of growvth hormone, cortisol, and catecholamines, as well as the accompanying changes in glucagon and insulin secretion.…”