BLOOD GLUCOSE LEVEL IN MICE

Abstract

ABSTRACT The hypoglycaemic effect of synthetic tetraicosapeptide corticotrophin was investigated in NMRI mice in order to determine its physiological significance as well as its mechanism of action. It was found that in normal non-fasting mice corticotrophin produced a maximal hypoglycaemic response at a dose level of about 5 μg per 20 g mouse (1250 milliunits per 20 g mouse). The ED50 of the hypoglycaemic effect was about 1000 times larger than the ED50 for adrenal cortical stimulation. Immunoassayable insulin was markedly increased 15 minutes following 5 μg of corticotrophin, whereas following a maximal steroidogenic dose (1.6 nanogram) or following ether stress the plasma insulin levels were normal. In adrenalectomized mice the administration of 5 μg of corticotrophin had practically no effect on the blood glucose level, whereas pretreatment with a glucocorticosteroid in adrenalectomized mice markedly restored the hypoglycaemic response. Acutely hypophysectomized mice showed a hypoglycaemic response to corticotrophin indistinguishable from that found in normal mice, whereas animals hypophysectomized 3–7 days before corticotrophin injection showed a smaller response. Corticotrophin in a dose of 5 μg per 20 g mouse had no hypoglycaemic effect in mice with manifest alloxan diabetes. Corticotrophin injected 5 minutes following a diabetogenic dose of alloxan hardly had any measurable effect on the acute initial alloxan hyperglycaemia, whereas the latter was greatly reduced when corticotrophin was given 5 minutes before alloxan administration. Pretreatment with corticotrophin did not change the frequency or intensity of the ensuing diabetic condition in mice. It is concluded that the corticotrophin induced hypoglycaemia is dependent on 1) the presence of normally functioning pancreatic beta-cells; and 2) the presence of glucocorticosteroids. It is doubtful whether the observed hypoglycaemia has any physiological significance.