Chronic streptozotocin diabetes in rats facilitates the acute stress response without altering pituitary or adrenal responsiveness to secretagogues

Endocrinology. 1991 Jul;129(1):99-108. doi: 10.1210/endo-129-1-99.


We have used streptozotocin (STZ)-induced diabetes in rats to determine whether this represents a sustained stimulus to the adrenocortical system and whether STZ-diabetic rats are able to mount an acute stress response. Furthermore, we compared pituitary responsiveness to CRF and/or arginine vasopressin, and adrenal responsiveness to ACTH in STZ- vs. vehicle-treated rats. We also compared the efficacy of dexamethasone inhibitory feedback in STZ-diabetic and control rats. Our results show that STZ-treated rats chronically hypersecrete corticosterone (B) as evidenced by their decreased thymus weights, their increased urinary B excretion, and their elevated mean plasma B levels during the light hours of the day. Despite the evidence for sustained hypersecretion of B, STZ-treated rats showed greater and more prolonged ACTH and B responses to the acute stress of histamine injection. However, when tested separately, neither pituitary nor adrenal responsiveness to their secretagogues were increased in STZ-diabetic compared to control rats. Dexamethasone inhibition of stress-induced B secretion was tested using two different paradigms: pentobarbital-anesthetized rats were given iv injections of acid saline, and awake rats were given ip injections of histamine. In both experiments the STZ-treated rats were relatively resistant to glucocorticoid inhibition of stress responses. This finding, taken together with the exaggerated ACTH and B responses to stress, strongly suggests that the facilitatory effects of chronic STZ-diabetes are a consequence of changes in sensitivity of central neural components of the adrenocortical system to stimulatory and/or inhibitory inputs, in conjunction with changes in glucocorticoid feedback sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Glands / drug effects
  • Adrenal Glands / metabolism*
  • Adrenocorticotropic Hormone / metabolism
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Arginine Vasopressin / pharmacology
  • Circadian Rhythm
  • Corticosterone / blood
  • Corticosterone / urine
  • Corticotropin-Releasing Hormone / pharmacology
  • Dexamethasone / pharmacology
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / physiopathology*
  • Histamine / pharmacology
  • Male
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Stress, Physiological / complications
  • Stress, Physiological / physiopathology*


  • Arginine Vasopressin
  • Dexamethasone
  • Histamine
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone