Evidence for the paracrine action of islet-derived corticotropin-like peptides on the regulation of insulin release
| Autor: | Fernando E. Estivariz, Juan José Gagliardino, María Inés Borelli |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Pro-Opiomelanocortin Endocrinology Diabetes and Metabolism medicine.medical_treatment Endogeny Biology Islets of Langerhans chemistry.chemical_compound Endocrinology Adrenocorticotropic Hormone Proopiomelanocortin Neutralization Tests Internal medicine medicine Animals Insulin Rats Wistar Pancreatic hormone geography geography.geographical_feature_category Pancreatic islets Metabolism Islet Rats medicine.anatomical_structure L-Glucose chemistry biology.protein Peptides hormones hormone substitutes and hormone antagonists |
| Zdroj: | Metabolism. 45:565-570 |
| ISSN: | 0026-0495 |
| DOI: | 10.1016/s0026-0495(96)90025-6 |
| Popis: | 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 1–39 ACTH 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 1–39 ACTH 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. |
| Databáze: | OpenAIRE |
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