Showing papers by "Rüdiger Göke published in 1989"
TL;DR: The data demonstrate an additive synergistic effect of GLP‐ 1 and GIP on the glucose‐induced insulin release, which supports the concept of an action ‘in concert’ of gastrointestinal incretin hormones postprandially released on the endocrine pancreas to guarantee adequate insulin answers after meals.
61 citations
TL;DR: The effect of guanine nucleotides on binding of GLP-1(7-36)amide indicates that the action of the peptide is mediated by the adenylate cyclase system, making an involvement of the inositol 1,4,5-trisphosphate pathway or an activation of protein kinase C in the postreceptor signaling after GLP (7- 36)amide binding unlikely
Abstract: Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide], probably representing an important incretin, binds to receptors on RINm5F cells resulting in an adenosine 3',5'-cyclic monophosphate increase. Guanine nucleotides (GTP, GTP-gamma-S, GDP-beta-S) decreased the binding of GLP-1(7-36)amide to receptors on RINm5F cell membranes. Further analysis revealed that GTP (10(-4) M) decreased the receptor affinity with an increase of the Kd from 2.5 +/- 0.99 x 10(-10) M to 9.43 +/- 2.16 x 10(-10) M. In cross-linking experiments the amount of labeled peptide linked to receptors was reduced in the presence of GTP (10(-4) M). Further studies investigated the involvement of membrane depolarization or changes in the cytosolic free calcium level in the intracellular signaling of GLP-1(7-36)amide-induced insulin secretion. In contrast to fuel and nonfuel secretagogues, GLP-1(7-36)amide did not cause a depolarization of the membrane potential. This was unaffected by various glucose concentrations (0-20 mM) or by previous cell depolarization by D-glyceraldehyde. Similarly, the cytosolic calcium concentration remained unchanged after addition of GLP-1(7-36)amide (10(-12)-10(-8) M). The effect of guanine nucleotides on binding of GLP-1(7-36)amide indicates that the action of the peptide is mediated by the adenylate cyclase system. GLP-1(7-36)amide binding neither changed the membrane potential nor altered the intracellular calcium concentration, making an involvement of the inositol 1,4,5-trisphosphate pathway or an activation of protein kinase C in the postreceptor signaling after GLP-1(7-36)amide binding unlikely.
50 citations
TL;DR: It is proposed that all four insulins arise from a single proinsulin by proteolytic cleavages at different sites within the C-peptide region.
40 citations
TL;DR: The present data allow the conclusion that the somatostatin action upon GLP-1(7–36)amide effects is at least partly related to regulation of intracellular cyclic nucleotides.
Abstract: Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide], a new important incretin candidate, binds to specific high-affinity receptors on rat insulinoma-derived beta-cells (RINm5F). In the present study, the effect of somatostatin-14 on the GLP-1(7-36)amide-induced insulin release and cAMP generation in this cell line was investigated. Somatostatin did not decrease basal insulin release of RINm5F cells. The GLP-1(7-36)amide-induced insulin release was decreased concentration dependently by somatostatin. Somatostatin, 1 microM reduced the maximally GLP-1(7-36)amide-stimulated (0.1 microM) insulin release to basal insulin levels. The GLP-1(7-36)amide-induced cAMP production was significantly decreased by somatostatin in a concentration-dependent manner. The GLP-1(7-36)amide concentration causing half-maximal cAMP production was 2.98 +/- 1.56 nM. Somatostatin left the EC50 unaltered but decreased the maximal GLP-1(7-36)amide effect for 32% in the presence of 1 nM somatostatin and for 50% at 1 microM. In additional experiments, the interaction of both hormones was evaluated in the perfused pancreas as a nontumor model. Somatostatin (1 nM, 1 microM) inhibited the glucose-induced (6.7 mM) and GLP-1(7-36)amide-potentiated (0.05, 0.5, and 5 nM) insulin release dose dependently. The biphasic pattern of insulin release remained preserved. The GLP-1(7-36)amide-induced insulin release is potently inhibited by somatostatin-14. This effect was demonstrated in different model systems for beta-cell function studies. The present data allow the conclusion that the somatostatin action upon GLP-1(7-36)amide effects is at least partly related to regulation of intracellular cyclic nucleotides.
33 citations
TL;DR: It is demonstrated that SCLC cell lines release IGF-BPs in culture supernatants, which differ from IGF- BPs detected in liver and placenta, which might be important mediators in the autocrine/paracrine growth regulation of IGFs in S CLC.
26 citations
16 citations
TL;DR: It is concluded that a partial phosphorylation of insulin receptors and a submaximal tyrosine kinase activation are sufficient for full stimulation of glucose transport in the adipocyte and suggested that negative cooperativity of the insulin receptor and activation of its tyrosin kinase require a similar conformational change of the receptor protein.
13 citations
TL;DR: HLC-supported analysis of cell content after internalization of125I-GLP-1(7–36)amide during a 60-min incubation period at 37°C revealed an elution profile showing two maxima of radioactivity: one represented intact labeled GLP- 1(7-36), the other an intracellular degradation product of the peptide.
Abstract: Glucagon-like peptide-1(7-36)amide [GLP-1(7-36)amide] is supposed to be an important physiologic incretin. Recently, high affinity receptors for GLP-1(7-36)amide have been demonstrated on rat insulinoma-derived RINm5F cells. The present study examined the internalization and degradation of the GLP-1-receptor complex. Internalization of the peptide was time- and temperature-dependent. At 37 degrees C binding and internalization was rapid. At 60 min 35% of 125I-labeled GLP-1(7-36)amide was internalized. Incubation in the presence of increasing concentrations of non-labeled GLP-1(7-36)amide resulted in a decrease of internalization of 125I-labeled peptide indicating that this process is saturable. Incubation in the presence of 0.2 mM chloroquine, an inhibitor of intracellular hormone degradation, resulted in intracellular accumulation of 125I-GLP-1(7-36)amide. HPLC-supported analysis of cell content after internalization of 125I-GLP-1(7-36)amide during a 60-min incubation period at 37 degrees C revealed an elution profile showing two maxima of radioactivity: one represented intact labeled GLP-1(7-36)amide, the other an intracellular degradation product of the peptide. Chloroquine caused a 5-fold increase of the peak representing intact 125I-GLP-1(7-36)amide thus demonstrating inhibition of degradation of labelled peptide. Furthermore, a 4-fold increase of the other peak occurred possibly mirroring a delay of release of degradation products by chloroquine. It was excluded that chloroquine is able to interfere with GLP-1(7-36)amide-binding to its receptor.
12 citations
TL;DR: The findings exclude a direct effect of camostate on the secretory process of pancreatic acinar cells, however, after repeated oral pretreatment of donor rats a “desensitization” of acini against cerulein stimulation occurs.
Abstract: Oral administration of the proteinase inhibitor camostate to rats results in a characteristic regulation of pancreatic enzyme synthesis and release. These effects are thought to be mediated by an endogenous cholecystokinin release in answer to camostate feeding. An additional direct effect of the compound could be exerted directly on the acinar cell. We evaluated in the present study whether the acute or chronic influence of camostate alters the basal or cerulein-stimulated enzyme release from isolated rat acini.
9 citations