title: Evidence for the paracrine action of islet-derived corticotropin-like peptides on the regulation of insulin release.
abstract: In view of recent evidence for the endogenous synthesis of proopiomelanocortin (POMC) by pancreatic islets, we have assessed (1) the release of POMC-derived corticotropin (ACTH)-like peptides (ACTH-LP) from isolated perifused rat islets, and (2) the potential paracrine modulatory effect on insulin output of these putative secretagogues. Islets perifused at a glucose concentration of 3.3 mmol/L secreted ACTH-LP at 0.15 +/- 0.005 ng/islet/10 min, which was increased by 17-fold at 16.7 mmol/L glucose. Islets statically incubated with different concentrations of medium glucose plus synthetic 1-39ACTH at 55 pmol/L showed a significant increase of insulin release at 8 (by 79%) and 16 (by 119%) mmol/L glucose, but not at 4 mmol/L. To determine the possible cis-directed effects of these endogenously released islet ACTH-LP on insulin secretion, we either blocked their biological action by immunoneutralization with an ACTH-specific antiserum or prevented their receptor interaction by addition of the ACTH-inhibiting polypeptide (CIP) to the incubation medium. In the presence of 16.7 mmol/L glucose, the rate of insulin output decreased by approximately 25% upon exposure to the antiserum and by approximately 50% in the presence of CIP. The foregoing observations would therefore suggest that both (1) the elaboration of ACTH-LP by isolated perifused islets and (2) the stimulation of islet insulin release by exogenous 1-39ACTH in static incubation occur as a function of glucose concentration in the incubation medium, and that (3) the newly-secreted endogenous ACTH-LP operate in a cis mode to enhance islet insulin output in a manner analogous to that of exogenously added ACTH species. These results strongly support the view that islet-elaborated ACTH-LP are important physiological paracrine modulators of insulin secretion.
authors.affiliation: Centro de Endocrinologia Experimental y Aplicada, Universidad Nacional de La Plata, Argentina.
authors.forename: M I
authors.initials: MI
authors.lastname: Borelli
authors.forename: F E
authors.initials: FE
authors.lastname: Estivariz
authors.forename: J J
authors.initials: JJ
authors.lastname: Gagliardino
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009500:Neutralization Tests; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D010455:Peptides; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone