INFLUENCE OF SOMATOTROPHIN AND CORTISONE ON THE INSULIN SENSITIVITY OF RATS12

Abstract

The hypoglycemic response to insulin (0.1-1.0 unit/kg body weight given intraperitoneally after 24 hours of fasting) was determined in rats subjected to various experimental procedures. Our "standard" regimens of somatotrophin (STH) and cortisone (STH: 0.5 mg Armour standard equivalent/100 g body weight daily for 5 days; cortisone: 0.5 mg/100 g body weight daily for 5 days) were not individually effective on either fasting blood sugar or insulin sensitivity of intact rats, whereas fasting hyperglycemia and a greater absolute drop of blood sugar in response to insulin occurred when a combined STH-cortisone regimen was given. Hypophysectomized rats showed low fasting blood sugar levels and a greatly exaggerated sensitivity to insulin. The standard dose (SD) of STH and smaller quantities of cortisone (0.1 of the SD), while having no or little effect on the fasting hypoglycemia, partially counteracted the insulin sensitivity of such animals. When the standard regimen of cortisone was given, the insulin sensitivity of hypophysectomized rats increased as the fasting blood sugar became higher than normal. STH and cortisone exerted opposite effects on the fasting blood sugar level of hypophysectomized rats (in contrast to their action in intact animals). However, there was a marked synergism between these hormones with regard to insulin-antagonism in hypophysectomized rats. Ad-renalectomized rats also displayed fasting hypoglycemia and enhanced insulin sensitivity. Cortisone (SD) restored fasting blood sugar and insulin sensitivity of these animals to normal, whereas the standard STH regimen had no effect on either. STH was also ineffective when given in conjunction with incomplete replacement therapy with cortisone. Hypophysectomized-adrenalectomized rats, and hypophysectomized-sham adrenalectomized controls, showed lower fasting blood sugar levels than hypophysectomized rats, and a remarkably sluggish - but nevertheless greatly exaggerated - blood sugar response to insulin. STH (SD) protected hypophysectomized-adrenalectomized rats against the hypoglycemic effects of insulin, without affecting the fasting hypoglycemia. The metabolic defect which leads to insulin sensitivity is not the same in hypophysectomy and in adrenalectomy, since the insulin sensitivity of hypophysectomized animals is synergistically alleviated by STH and cortisone, whereas that of adrenalectomized animals responds only to cortisone therapy.