Effects of preproglucagon-derived peptides and exendins on steroid-hormone secretion from dispersed adrenocortical cells of normal and streptozotocin-induced diabetic rats.

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.

• Authors: Ludwik K Malendowicz, Raffaella Spinazzi, Gastone G Nussdorfer, Marcin Trejter
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 12 Issue 1 Pg. 115-9 (Jul 2003) ISSN: 1107-3756 [Print] Greece
• PMID: 12792820 (Publication Type: Journal Article)

Chemical References

• Peptides
• Protein Precursors
• Steroids
• Proglucagon
• Adrenocorticotropic Hormone
• Glucagon

Topics

• Adrenal Cortex (metabolism)
• Adrenocorticotropic Hormone (metabolism)
• Animals
• Diabetes Mellitus, Experimental (metabolism)
• Glucagon (metabolism)
• Peptides (metabolism)
• Proglucagon
• Protein Precursors (metabolism)
• Rats
• Steroids (metabolism)