Abstract:
:Many lines of evidence have shown that preproglucagon-derived peptides affect steroid secretion from dispersed adrenocortical cells, and that streptozotocin (STZ)-induced experimental diabetes alters adrenocortical-cell function. Hence, we compared the effects of glucagon, glucagon-like peptide (GLP)-1 and GLP-2 on basal and ACTH-stimulated secretion of dispersed adrenocortical cells from normal and STZ-induced diabetic rats. We also examined the effects of exendins (EX) 3 and 4, because EX4 is known to be a potent and long-lasting agonist of GLP-1 receptors. STZ-induced diabetes moderately enhances basal and ACTH-stimulated secretion from dispersed zona glomerulosa (ZG) cells, without significantly affecting corticosterone production from dispersed zona fasciculata-reticularis (ZF/R) cells. In normoglycemic rats, glucagon increased basal aldosterone and corticosterone secretion from ZG and ZF/R cells, GLP-2 raised both basal and ACTH-stimulated aldosterone secretion and ACTH-stimulated corticosterone output, and EX4 increased basal corticosterone secretion. In contrast, glucagon, GLP-2 and EX4 did not elicit secretory responses from adrenocortical cells of diabetic rats. GLP-1 and EX3 did not alter secretion of dispersed adrenocortical cells of either normal or STZ-treated rats. Taken together, our findings indicate that preproglucagon-derived peptides enhance steroid secretion from adrenocortical cells of normal, but not STZ-induced diabetic rats. It is suggested that the prolonged exposure to low concentrations of insulin causes unresponsiveness of adrenocortical cells to glucagon, GLP-2 and EX4, which may contribute to the hyporeninemic hypoaldosteronism and alterations in glucocorticoid metabolism occurring in experimental diabetes.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Malendowicz LK,Spinazzi R,Nussdorfer GG,Trejter Msubject
Has Abstractpub_date
2003-07-01 00:00:00pages
115-9issue
1eissn
1107-3756issn
1791-244Xjournal_volume
12pub_type
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