Diabetes is a chronic metabolic disease whose incidence is increasing over the years in countries. Uncontrolled or poor controlled diabetic patients present several secondary complications induced by hyperglycemia, which are involved with the high morbidity and mortality of this disease. Moreover, the reduction of insulin production in diabetic patients induces an increase of the activity of HPA axis that results in an increase of glucocorticoid production has been described in patients with diabetes mellitus and in animal models of this disease in other research. To investigate the effect of hyperglycemia on the hypothalamic-pituitary-adrenal axis in an attempt to link between hyperglycemia and stress hormones and estimate the responsiveness of adrenal to exogenous adrenocorticotrophic hormone (ACTH) in inducing Type 1 Diabetes (T1D) rat. Twenty-six Wistar Albino rats (Male) were randomly grouped into two groups, negative control Group I and Group II were treated with 160 mg/kg intraperitoneal injection of alloxan and served as type 1 diabetes experimental model. This study was designed as ex-vivo and in vitro study, The following features were measured: fasting and random blood sugar at zero-day, then at the end of the 4th week; at sacrificed day, serum corticosterone, and serum ACTH were measured by ELISA kits after blood sampling from the heart. In vitro study, the rats were anesthetized by diethyl ether and sacrificed by decapitation and then dissected and adrenal glands were isolated, then incubated and the solution that bathed adrenal gland was collected before and after adding ACTH. The samples were frozen at -20c then corticosterone were measured by ELISA. Results: The results demonstrated that fasting and random blood glucose levels after 4weeks were highly significant in Alloxan-induced T1D group in comparison with control, The weight of the adrenal gland was significantly increased and accompanied with a significant increase in serum corticosterone level & serum ACTH level in Alloxan-induced T1D group as compared to control. There were positive correlations between fasting blood glucose with serum ACTH and serum corticosterone in Alloxan treated rats. also In vitro study, spontaneous secretion of corticosterone without and with exogenous ACTH stimulation of adrenal gland resulted in significant increase in Alloxan treated rats compared with the control group but still this increment of corticosterone secretion before and after (ACTH) stimulation is less (only 1.52 folds) in Alloxan treated rats than corresponding control group (2.96 folds). Hypercortisolismis initiated by an augmented release of ACTH under the effect of hyperglycemia on hypothalamic-pituitary axis leading subsequently to hypertrophy of adrenal gland in alloxan-treated rats and a decrease in vitro responsiveness of adrenal cortex to exogenous ACTH in T1D was observed.
(FULL ARTICLE LINK) Read more ...
2018
|
|
|
