Disturbance of the Feedback Mechanism of the Adrenocortical System in the Alloxan Diabetic Rat

Langholz, J.; Lage, Mary

doi:10.1530/acta.0.072s031

Cited by 1 publication

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“…In our study, not only was there a marked difference in the magnitude of pituitaryadrenal responses between control and diabetic animals, but these responses also terminated significantly more rapidly in control and insulin-treated diabetic rats than in diabetic animals. This is likely the result of decreased glucocorticoid negative-feedback sensitivity in diabetic rats (30,40,41). Thus, both activation and termination of the pituitary-adrenal response to hypoglycemia are impaired in the early stages of STZ-induced diabetes.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Impairs Hypothalamo-Pituitary-Adrenal (HPA) Responses to Hypoglycemia, and Insulin Treatment Normalizes HPA but not Epinephrine Responses

Chan

Inouye

et al. 2002

Diabetes

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We recently established that in addition to plasma adrenocorticotrophic hormone (ACTH) and corticosterone, hypothalamic corticotrophin-releasing hormone (CRH) mRNA and hippocampal type 1 glucocorticoid receptor (GR1) mRNA were also upregulated in uncontrolled streptozotocin-induced diabetes. In the current study, control, diabetic, and insulin-treated diabetic rats underwent a hyperinsulinemic-hypoglycemic glucose clamp to evaluate central mechanisms of hypothalamo-pituitary-adrenal (HPA) and counterregulatory responses to insulininduced hypoglycemia. Increases in plasma ACTH, corticosterone, and epinephrine were significantly lower in diabetic rats versus controls. Insulin treatment restored ACTH and corticosterone but not epinephrine responses to hypoglycemia in diabetic rats. Glucagon and norepinephrine responses to hypoglycemia were not affected by diabetes or insulin treatment. In response to hypoglycemia, hypothalamic CRH mRNA and pituitary proopiomelanocortin mRNA expression increased in control and insulin-treated but not in untreated diabetic rats. Arginine vasopressin mRNA was unaltered by hypoglycemia in all groups. Interestingly, hypoglycemia decreased hippocampal GR1 mRNA expression in control and insulintreated diabetic rats but not in diabetic rats. In contrast, type 2 glucocortoid receptor (GR2) mRNA was not altered by hypoglycemia. In conclusion, despite increased basal HPA activity, HPA responses to hypoglycemia were markedly reduced in uncontrolled diabetes. We speculate that the defect in CRH response could be related to the defective GR1 response. It is intriguing that insulin treatment restored the HPA response to hypoglycemia but, surprisingly, not the deficient epinephrine response. This is important because during severe hypoglycemia, epinephrine is an important counterregulatory hormone. Diabetes

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Section: Discussionmentioning

confidence: 99%