Hypophysectomized, adrenalectomized, and adrenal enucleated rats, maintained on a normal or a diabetogenic high-fat, high-protein diet, were used to investigate the role of the pituitary-adrenal axis on reduced B-chain-albumin induced hyperglycemia. Hypophysectomized and adrenal enucleated rats maintained on a normal diet did not show a reduced B-chain induced hyperglycemia, while adrenalectomized rats showed a significant hypoglycemia. Hypophysectomized, and adrenalectomized rats kept on a diabetogenic diet were insensitive to reduced B-chain hyperglycemia, but adrenal enucleated rats showed a significant hyperglycemia. These results indicate that the secretions of the adrenal cortex but not the adrenal medulla are involved in reduced B-chain-albumin induced hyperglycemia. Growth hormone and adrenocorticotrophic hormone replacement experiments with hypophysectomized rats kept on the diabetogenic diet indicated that while ACTH plays the more important role, the functioning of both of these hormones is necessary for reduced B-chain elicited hyperglycemia. Adrenalectomized rats on the diabetogenic diet and treated with corticosterone showed a significant and persistent B-chain induced hyperglycemia, demonstrating further that adrenocortical glucocorticoids are involved in this mechanism. The specificity of reduced B-chain induced hyperglycemia is demonstrated by the observation that the reduced A chain of insulin does not elicit this effect but instead induces a moderate but significant hypoglycemia.

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