The effects of stress and injury on the activity of phosphoenolpyruvate carboxykinase in the liver of the rat

Abstract

The effects of stress (diethyl ether anaesthesia for 4-8 min, or intravenous injection of 0.05 ml of a dimethyl sulphoxide/water mixture) and of a scald injury given under ether anaesthesia on hepatic PEPCK (phosphoenolpyruvate carboxykinase, EC 4.1.1.32) were studied in the post-absorptive rat. Injury raised PEPCK activity by about 70% in 2 h and by over 100% in 4 h, over three times as fast as in animals that had only been handled (controls). The two stresses, both of types commonly imposed in animal experiments, had almost as much effect as injury for the first 2 h, although much less thereafter. The roles of sympathetic stimulation and corticosterone in mediating these rises were studied by using alpha beta-blockers and trilostane respectively as inhibitors. (Trilostane only decreased corticosterone concentrations to a little above control values.) The ether-induced increase was somewhat decreased by alpha beta-blockade, but was only eliminated by combined alpha beta-blockade and trilostane. After injury, however, PEPCK synthesis was unaffected by either alpha beta-blockade or trilostane, although it was decreased by their combined action; and it seems that either corticosterone or sympathetic stimulation was sufficient to stimulate PEPCK synthesis maximally. Stimulation by corticosterone was much greater than reported previously by others, for reasons that are discussed. Sympathetic stimulation may have been mediated by glucagon and cyclic AMP, since injury raised portal glucagon concentrations, and stress and injury raised those of hepatic cyclic AMP. PEPCK synthesis was, however, stimulated despite increases in portal insulin concentration, and was not related to the [insulin]/[glucagon] ratio. Thus stress and injury over-rode normal control mechanisms.

Glucose, insulin and other plasma metabolites shortly after injury.

“…Values (Fig. 4) were higher in women than in men at ISS 4-8 (P<0.05) and [9][10][11][12][13][14] (P < 0.005), as expected,11 and rose with time after injury at ISS [4][5][6][7][8][9][10][11][12][13][14] [adrenaline] had been measured in them. The residuals were, however, very non-normally distributed.…”

“…2), which were measured within the fairly narrow bands of injury severity shown. These, suggested by Copes et al,13 correspond to minor (ISS 1-3), moderate (4)(5)(6)(7)(8), severe (9)(10)(11)(12)(13)(14), very severe (16)(17)(18)(19)(20)(21)(22)(23)(24) and life-threatening (25+) injuries. Success has been measured by the percentage of the variance within each group that can be accounted for by the various factors.…”

“…6 The rise in [glucagon] probably contributes to the maintenance of hyperglycaemia,7 although the [glucagon]/[insulin] ratio is not raised. 8 If this theory is correct then it should be able to account for the values of [glucose] that are measured in patients following injury. Failure would indicate that this theory is inadequate, however well it is supported by the results of controlled experiments in animals.…”

Hormonal Control of Metabolism in Trauma and Sepsis

“…Of these, adrenaline seems to play the major role after injury, since the resultant hyperglycaemia is fairly closely related to plasma adrenaline concentrations . Glucagon secretion after injury is largely 8-adrenergically mediated (Porte & Robertson, 1973;Lindsey et al, 1975;Rose & Heath, 1986) and so might be involved in this relationship, but several studies have shown that glucagon secretion responds relatively slowly to injury (e.g. Meguid el al., 1972; Giddings et al, 1976; see also Fig.…”