Showing papers by "Rüdiger Göke published in 1990"

Interaction of glucagon-like peptide-1 (7-36)amide and cholecystokinin-8 in the endocrine and exocrine rat pancreas.

Abstract: Summary The synergistic impact of glucagon-like peptide-1 (GLP-1) (7–36)amide and cholecystokinin-8 (CCK-8) was studied in the rat pancreas. The GLP-1 (7–36)amide (1 pM-1μM) had no effect on the basal or CCK-stimulated (1 nM-1 pM) amylase release from isolated pancreatic acini. The insulinotropic action of 0.5 nM GLP-1 (7–36)amide, which weakly stimulated the glucoseinduced (6.7 mM) insulin release from the isolated perfused rat pancreas, was strongly potentiated by the addition of CCK-8 (20, 50, and 100 pM) to the perfusate. In concentrations as they occur physiologically after a meal, CCK-8 alone had no significant effect on basal or glucose-stimulated (6.7 mM) insulin secretion. Our data support the assumption that the nutrient-regulated intestinal release of various peptides represents a regulatory system to ensure an adequate insulin response to food intake, at least in rats.

Dexamethasone pretreatment of rat insulinoma cells decreases binding of glucagon-like peptide-1(7-36)amide.

Abstract: The effect of dexamethasone on binding of glucagon-like 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 GLP-1(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.

Atrial natriuretic factor has a weak insulinotropic action in the isolated perfused rat pancreas.

Abstract: The effect of atrial natriuretic factor (ANF; 1, 10, 100, 1000 pmol/l) on insulin release from the isolated perfused rat pancreas was studied. ANF weakly augmented the glucose (10 mmol/l)-stimulated insulin release during the second (controls: 100%; 1 pmol/l: 99%; 10 pmol/l: 149%, P<0.05; 100 pmol/l: 111%; 1000 pmol/l 135%), but not the first phase of the secretory response. In contrast, the first, but not the second phase of arginine (10 mmol/l)-stimulated insulin release was significantly enhanced by ANF (1000 pmol/l; controls: 100%; 1000 pmol/l: 235%, P<0.05). The hormone did not influence basal insulin secretion. Our data indicate an insulinotropic effect of ANF on the rat pancreas, which is dependent on the utilized background secretagogues.

Carbachol priming increases glucose- and glucagon-like peptide-1 (7-36)amide-, but not arginine-induced insulin secretion from the isolated perfused rat pancreas.

Abstract: The priming effect of carbachol on glucose-, arginine- and glucose plus GLP-1 (7-36)amide induced insulin secretion was investigated. The isolated rat pancreas was perfused in vitro during a basal period of 10 min with Krebs-Ringer-bicarbonate buffer containing 2.8 mmol/l glucose. This medium was then supplemented with carbachol (10,1.0.1 mumol/l, respectively). After an additional 10 min period at 2.8 mmol/l glucose insulin secretion was stimulated for 44 min with 10 mmol/l glucose, or glucose plus GLP-1 (7-36)amide (0.5 nmol/l), or arginine (10 mmol/l). Pretreatment with carbachol resulted in a concentration dependent sensitization of B-cells to a consecutive glucose load (10 mmol/l). Both phases of the biphasic insulin secretory response were significantly enhanced. Priming experiments followed by a subsequent combined glucose / GLP-1 (7-36)amide or arginine stimulation were performed with 10 mumol/l carbachol. Prior exposure of the pancrease to carbachol enhanced the glucose / GLP-1 (7-36)amide induced insulin release, but left the arginine stimulated secretion unaltered. Our data suggest that in the regulation of postprandial insulin release cholinergic sensitizing effects might be involved which are mediated by muscarinic receptors.

Effect of proglucagon-derived peptides on amylase release from rat pancreatic acini

Abstract: The present study examined systematically the effect of proglucagon-derived peptides on secretion of the exocrine rat pancreas. It was studied whether glucagon, oxyntomodulin, glucagon (19–29), glucagon (22–29), glucagon-like peptide 1 (7–36)amide, or glucagon-like peptide 2(1, 10, 100, 1000 pM, respectively) alters basal or cholecystokinin-8 (1, 10, 100 pM)-induced amylase release from isolated acini. None of the peptides showed any effect on basal or CCK-stimulated amylase secretion. Furthermore, binding studies utilizing labeled peptides excluded specific binding sites on rat acinar cells for glucagon or glucagon-like peptide 1 (7-36) amide. Our data argue against a direct role for proglucagon-derived peptides in the regulation of exocrine pancreatic secretion in rats.