Anti-Insulin Effect of Cortisol in Deep Hypoglycemia of the Rat: Sex Differences[*]

Abstract

Deep hypoglycemia was induced by administering a large dose of glucagon-free insulin (200 U/kg) followed by food deprivation to cortisol-pretreated and control rats. The anti-insulin effect of cortisol was investigated in terms of protecting rats from death due to hypoglycemia. The following results were obtained. 1) Pretreatment of rats with Cortisol (30 mg/kg daily) for either 3 or 7 days resulted in significantly higher survival of males (72-100%) than females (34-43%) after the administration of insulin. Under the same conditions all control rats died in hypoglycemic convulsions. Testectomy completely abolished the anti-insulin effect of Cortisol, whereas pretreatment of testectomized rats with testosterone partially restored the effect. Testosterone did not alter the response of female rats. 2) During insulin induced hypoglycemia cortisol-pretreated male rats maintained their blood glucose and liver glycogen concentrations at significantly higher levels than similarly treated females. 3) Liver glucose-6-phosphatase (G-6-Pase) activity was significantly higher in control male rats than in females. Cortisol treatment enhanced the enzymatic activity in males but not females. After administration of insulin there was a further increase of G-6-Pase activity in cortisol-pretreated male rats. 4) Fasting alone stimulated liver G-6-Pase activity, especially in females, to a greater extent than did Cortisol in fasting rats. Enzyme activity was unchanged following insulin administration to the above treated animals. These results suggest that the gluconeogenic capacity of cortisol-treated male rats is higher than in similarly treated females. This difference in gluconeogenic capacity may partially explain their better survival under hypoglycemic conditions.

Key words

Hypoglycemia - Insulin - Cortisol - Testosterone - Liver Glycogen - Liver Glucose-6-Phosphatase Activity

1 Supported by a grant (No. 816/3) from the Yugoslav Federal Research Fund. A preliminary report of parts of this work appeared in abstract form in Diabetologia 5: 51 (1969).

1 Supported by a grant (No. 816/3) from the Yugoslav Federal Research Fund. A preliminary report of parts of this work appeared in abstract form in Diabetologia 5: 51 (1969).

2 Present address: Department of Pharmacology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, U.S.A.