Effects of preproglucagon-derived peptides and exendins on steroid-hormone secretion from dispersed adrenocortical cells of normal and streptozotocin-induced diabetic rats.
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.
Malendowicz
Ludwik K
LK
Department of Histology and Embryology, Karol Marcinkowski University of Medical Sciences, PL-60781 Poznan, Poland.
Spinazzi
Raffaella
R
Nussdorfer
Gastone G
GG
Trejter
Marcin
M
D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D052336:Proglucagon; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D013256:Steroids / Q000378:metabolism*
D010455:Peptides; D011498:Protein Precursors; D013256:Steroids; D052336:Proglucagon; D000324:Adrenocorticotropic Hormone; D005934:Glucagon