I Gunn, D O'Shea, and SR Bloom
G. Richter, R. Göke, B. Göke, and R. Arnold
The effect of dexamethasone on binding of glucagonlike peptide-1(7–36)amide (GLP-1(7–36)amide) to rat insulinoma-derived cells (RINm5F) was investigated. Preincubation of RINm5F cells with dexamethasone (100 nmol/l) for 24 h resulted in a decrease of GLP1(7-36)amide binding to 55·0±8·16% (mean ± s.e.m.), incubation for 48 h to 39·1±1·76%, and for 72 h to 15·5±4·35% of maximal binding. The GLP-1(7–36)amide-induced stimulation of cyclic AMP (cAMP) production was significantly decreased to 61·03±7·4% of maximum production in cells pretreated with dexamethasone (100 nmol/l) for 48 h. The decreased binding was due to a reduction of the receptor number while the receptor affinity remained unchanged. These inhibitory effects on binding and cAMP formation induced by dexamethasone were completely abolished when the antiglucocorticoid RU 38486 (100 nmol/l) was added during preincubation with dexamethasone. RU 38486 alone had no effects. Our data suggest that the biological action of GLP-1(7–36) amide at the B-cell may be modified by glucocorticoids.
Journal of Endocrinology (1990) 126, 445–450
Isabella Artner, Yan Hang, Min Guo, Guoqiang Gu, and Roland Stein
factors have been shown to play fundamental roles in pancreas development and function, especially those linked to endocrine cell-specific expression of the hormones glucagon and insulin (reviewed by Sander & German 1997 , Servitja & Ferrer 2004
P Plaisancié, V Dumoulin, J-A Chayvialle, and J-C Cuber
Glucagon-like peptide-1 (GLP-1) is released from endocrine cells of the distal part of the gut after ingestion of a meal. GLP-1 secretion is, in part, under the control of hormonal and/or neural mechanisms. However, stimulation of the colonic L cells may also occur directly by the luminal contents. This was examined in the present study, using an isolated vascularly perfused rat colon. GLP-1 immunoreactivity was measured in the portal effluent after luminal infusion of a variety of compounds which are found in colonic contents (nutrients, fibers, bile acids, short-chain fatty acids (SCFAs)). Oleic acid (100 mm) or a mixture of amino acids (total concentration 250 mm), or starch (0·5%, w/v) did not increase GLP-1 secretion over basal value. A pharmacological concentration of glucose (250 mm) elicited a marked release of GLP-1 which was maximal at the end of infusion (400% of basal), while 5 mm glucose was without effect on secretion. Pectin evoked a dose-dependent release of GLP-1 over the range 0·1–0·5% (w/v) with a maximal response at 360% of basal when 0·5% pectin was infused. Cellulose or gum arabic (0·5%) did not modify GLP-1 secretion. The SCFAs acetate, propionate or butyrate (5, 20 and 100 mm) did not induce a significant release of GLP-1. Among the four bile acids tested, namely taurocholate, cholate, deoxycholate and hyodeoxycholate, the last one was the most potent at eliciting a GLP-1 response with a maximal release at 300% and 400% of the basal value when 2 and 20 mm bile acid were administered respectively. In conclusion, some fibres and bile acids are capable of releasing colonic GLP-1 in rats and may contribute to the secretory activity of colonic L cells.
Journal of Endocrinology (1995) 145, 521–526
D. J. O'Halloran, G. C. Nikou, B. Kreymann, M. A. Ghatei, and S. R. Bloom
Glucagon-like peptide (GLP)-1 (7–36)-NH2 is a peptide found in the mucosal endocrine cells of the intestine, and plasma levels of GLP-1 (7–36)-NH2 immunoreactivity show a rise after the ingestion of a fat or mixed-component meal. We investigated the effects of physiological infusion of GLP-1 (7–36)-NH2 on a submaximal gastric acid secretion in healthy volunteers at a rate known to mimic the observed postprandial rise in plasma concentrations. Corrected gastric acid output decreased to less than 50% and volume output to 33% of stimulated values. After the infusion, the secretion of gastric acid recovered immediately to preinhibition values. These results suggest a novel role for GLP-1 (7–36)-NH2 as a physiological inhibitor of gastric acid secretion in man.
Journal of Endocrinology (1990) 126, 169–173
Hongbin Liu, Yunshan Hu, Richard W Simpson, and Anthony E Dear
Niamh X Cawley, Guida Portela-Gomes, Hong Lou, and Y Peng Loh
, we extend those findings and show yapsin 1-like immunoreactivity exclusively in human pancreatic islet α-cells and that purified yapsin 1 can generate glucagon by processing proglucagon. These results suggest the presence of a yapsin 1-like
N M Whalley, L E Pritchard, D M Smith, and A White
Introduction Like many prohormones, proglucagon is processed in a cell type-specific manner. In the α-cells of the pancreas, proglucagon is processed to glucagon by prohormone convertase 2 (PC2), but it undergoes alternative processing in the L
insulin. Recent work on understanding the physiological function of proglucagon-derived peptides has renewed interest in glucagon-based therapeutics. One of these peptides is glucagon-like peptide-1 (GLP1), which is secreted from the L cells of the
Herbert A Schmid and Josef Brueggen
in clinical trials, as expected based on the physiological effect of natural somatostatin. Glucose homeostasis is a complex process regulated by the interactions of various hormones, including insulin, glucagon, and somatostatin (among others), plus