This work was performed to study the release of proopiomelanocortin (POMC)-derived peptides from isolated pancreatic islets and the effect of ACTH--a member of that peptide family--on insulin secretion. Islets were incubated with 3,3 and 16.6 mM glucose and insulin and ACTH-like products (ACTH-LP) were measured by radioimmunoassay. Glucose stimulated the simultaneous release of insulin and ACTH-LP, the ACTH-LP concentration being higher when assayed with an antibody reacting with the N-terminus of ACTH. However, the increment in this release in the presence of the higher glucose concentration was larger when measured with an antibody against the ACTH mid-portion. Thus, although the islets would release more of a smaller ACTH-LP, 16.6 mM glucose would selectively increase the release of peptides of larger molecular size. Islets incubated with different concentrations of synthetic ACTH (50-500 pg/ml) increased the release of insulin in a dose-dependent manner. These results suggest that the release of endogenous ACTH-LP could contribute to the paracrine regulation of insulin secretion.
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