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Third Division, Department of Medicine, University of Kobe, Kobe, Japan
(Received 21 November 1975)
It has been shown that glucagon secretion from the perfused rat pancreas is enhanced by arginine (Assan, Boillot, Attali, Soufflet & Ballerio, 1972) and suppressed by glucose (Gerich, Charles & Grodsky, 1974). However, the effect of fructose on glucagon secretion remains unclear, although fructose is known to potentiate glucose- and mannose-induced insulin secretion (Curry, Curry & Gometz, 1972; Curry, 1974). The present study investigated the effect of fructose on arginine-induced glucagon and insulin release in perfused rat pancreas.
The perfusion of isolated rat pancreas was performed by the procedure described by Grodsky, Batts, Bennett, Vcella, McWilliams & Smith (1963) with minor modifications. The splenic vessels were ligatured at the hilum, and the left gastric vessels were also ligatured. Perfusate (3·8% dextran and 0·25% bovine serum albumin in Krebs-Ringer-bicarbonate buffer) containing 2·8 mm-glucose (Expt 1),
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ABSTRACT
The effects of recombinant human interleukin (rhIL)-1α, -1β, 2 and 6 on the release of ACTH from the ACTH-producing tumour cell line AtT-20 of the mouse were studied during relatively long periods of incubation. Levels of ACTH in the media, measured by radioimmunoassay, were increased by the addition of rhIL-1α or -1β after latent periods of more than 4 h. RhIL-1α and -1β were almost equally potent in this experiment and the minimum, half-maximum and maximum effective concentrations of both rhIL-1α and -1β were about 0·1 pmol/l, 1–3 pmol/l and 10–100 pmol/l respectively. During incubation with rhIL-1β, immunoreactive ACTH levels and mRNA levels of the ACTH precursor pro-opiomelanocortin in cells also increased without apparent changes in the growth rate of the cells. Although the AtT-20 cells used in this study were quite insensitive to human/rat corticotrophin-releasing hormone (CRH), the cells showed a significant response to CRH after incubation with rhIL-1β. RhIL-6 showed similar effects to those of rhIL-1β on ACTH synthesis and release; increasing ACTH in cells and media after a certain latent period. On the other hand, rhIL-2 did not change ACTH levels in the AtT-20 cells in this study. These observations indicate that rhIL-1α, -1β and rhIL-6 have direct effects on ACTH-producing cells to stimulate the release and synthesis of ACTH after a latent period.
Journal of Endocrinology (1989) 122, 33–39
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ABSTRACT
We have examined the mechanism by which corticostatin-I (CS-I) acts to attenuate ACTH-induced steroidogenesis in rat adrenal cells. CS-I inhibited ACTH-induced corticosterone production in a dosedependent manner, without any effects on the basal corticosterone level in adrenal cells. When the cells were stimulated by 100 pg ACTH/ml, the minimum effective concentration of CS-I was 100 ng/ml, and 0.3–1.0 μg CS-I/ml produced a 50% reduction of the stimulated corticosterone production. The inhibitory effect of CS-I on ACTH-stimulated corticosterone production became apparent within 15 min of incubation, and the effect was reversed quickly by the removal of CS-I from the media. CS-I had no effect on angiotensin II-stimulated aldosterone production by adrenal zona glomerulosa cells. CS-I also did not affect cyclic AMP- or forskolin-stimulated corticosterone production. In an in-vitro binding study using 125I-labelled CS-I, CS-I showed considerable specific binding to rat adrenal cells, and the binding competed with ACTH in a dose-dependent manner. These experiments suggest that CS-I competes with ACTH on their binding sites and exerts an inhibitory effect on the adrenal cells.
Journal of Endocrinology (1990) 125, 287–292
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ABSTRACT
Advances in techniques in molecular biology have facilitated the research into endogenous opioids and related peptides in several ways. The organization and expression of genes and the primary structure of three precursor proteins of opioid peptides have been elucidated. These studies predicted the presence of potentially bioactive peptides, which has been confirmed by later studies. Advances in techniques in protein chemistry have helped to elucidate the distribution and molecular forms of endogenous opioids and related peptides in the body, and the processing of precursor proteins. Studies on the function of these peptides have shown a broad spectrum of actions. Leumorphin, a newly identified peptide, has been shown to exhibit unique biological activities. In spite of extensive studies, the physiological and pathophysiological significance of opioid peptide systems are not yet completely understood. This is mainly due to the paucity of our knowledge about opioid receptors. Further studies on the subtypes of opioid receptors will help to elucidate all aspects of the function of endogenous opioids and related peptides.
J. Endocr. (1985) 107, 147–157
