A Comparison of the Insulinotropic and the Insulin-Inhibitory Actions of Gut Peptides on Newborn and Adult Rat Islet Cells

Abstract

The objective of this study was to examine the release of insulin from cultured islet cells, taken from the pancreas of newborn and adult rats, in response to gastric inhibitory polypeptide (GIP), cholecystokinin-8 (CCK-g), calcitonin gene-related peptide (CGRP), and pancreastatin. GIP ( lo-' M) potentiated glucose-stimulated release of insulin in a dose-dependent fashion from both newborn and adult islet cells. CCK-8 (>lo-* M) also increased glucose-stimulated release of insulin from newborn islet cells, however its effect was not significant and not as strong as that observed with adult islet cells. Culture of newborn islet cells for 3 weeks with media containing high concentrations of glucose (16.7 mM) enhanced insulin release in response to CCK-8. CGRP did not affect the release of insulin from newborn islet cells, whereas at M, it reduced the release of insulin from adult islet cells by 66 _t 4%. Pancreastatin ( loe9-M) did not affect the release of insulin from newborn islet cells when cells were incubated with 4.2 mM glucose, whereas it stimulated the release of insulin from adult islet cells in a dose-dependent fashion. When incubated with 16.7 mM glucose, pancreastatin inhibited the release of insulin from both newborn and adult islet cells. These results indicate that newborn islet cells experience developmental changes which render them responsive to enteric peptides. Key Words: Insulin-Islet cell-Gastric inhibitory peptide (GIP)-Cholecystokinin-8 (CCK-8)-Calcitonin gene-related peptide (CGRP)-Pancreastatin.The effects of aging on the release of insulin from the pancreas have been studied before, but most earlier studies have concentrated on glucosestimulated release of insulin and on a comparison of insulin secretion in young adult rodents with that of senescent rodents (1-3). Several gut peptides have either insulinotropic or insulin-inhibitory actions (4), however, whether their actions are modified by aging is not known. In this study, we compared the effect of the following gut peptides on the release of Manuscript received May 27, 1987; revised manuscript acinsulin from cultured newborn and adult rat islet cystokinin-8 (CCK-8), calcitonin gene-related peptide (CGRP), and pancreastatin. Pancreastatin is a new peptide that was extracted from the porcine pancreas by Tatemoto and colleagues (5,6); it con-

The spectrum of endogenous human chromogranin A-derived peptides identified using a modified proteomic strategy

“…This peptide has multiple properties in that it inhibits insulin secretion from pancreatic islets [22,23], amylase release from the exocrine pancreas [24] and acid secretion from gastric fundus parietal cells [25]. The primary structure of human pancreastatin was deduced from the cloned cDNA of human CgA [11], corresponding to a 52 amino acid residue, C-terminally amidated peptide (residues 250-301].…”