Inhibitory effect of glucagon on erythropoiesis.

The effect of glucagon on erythropoiesis has been studied in mice and rats. Long-acting glucagon protamine zinc (Novo) was injected subcutaneously twice daily at 9 a.m. and 4 p.m. After administration of 2 x 200 ag/day for 10 days, the erythropoiesis of male rats was markedly depressed. Total normoblasts counts per femur. reticulocytes. and “Fe uptake into red cells fell respectively to 35%, 50%, and 1 7% of control values. The same results were observed with male and female mice injected twice daily with 50 g of glucagon. The erythropoietic response of mice to hypoxia was also inhibited. After 12 days of hypoxia. (320 mm Hg 16 hr/day). the red cell mass increased in controls from 3.12 to 6.31 and only to 5.19 ml/100 g body weight in the glucagon-treated group (p < 0.02). Response of polycythemic mice to exogenous erythropoietin (ESF) was reduced after glucagon injection. and the inhibition was proportional to the logarithm of the dose. The lowest active dose (3 gig) reduced the “Fe uptake to 77% of controls. whereas 50 g administration reduced it to 43%. This inhibitor effect decreased gradually as a function of the time interval between glucagon injections and ESF administration. Production of ESF seemed unaffected by glucagon administration. since after hypoxia (4 hr. 300 mm Hg). the ESF titer of rats and mice was similar in controls and glucagon-treated groups. As the inhibitory effect of glucagon was only elicited if administrated close to the ESF injection. and since no effect on ESF production could be demonstrated. it was inferred that the hormone acts mainly at the level of erythrod stem cell differentiation. It was suggested that hyperglucagonemia was responsible for the anemia of glucagonomas and might be implicated in the anemia of other clinical conditions.