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Oxyntomodulin and related peptides control somatostatin secretion in RIN T3 cells
T Tani1, A Le Quellec, C Jarrousse
1Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Abstract:
We studied the effects of oxyntomodulin (OXM), of its C-terminal (19-37) fragment (OXM (19-37)) and of glucagon (GLU) on somatostatin release, cyclic AMP accumulation and inositol phosphate turnover in somatostatin-secreting RIN T3 cells in culture. Rapid changes in cellular free Ca2+ were also measured using fura-2. Carbachol was used as a control test agent for the parameters involving the inositol phosphate/Ca2+ cascade. OXM, GLU and OXM (19-37) were all able to stimulate somatostatin release with relative ED50 of approx. 1, 22 and 45, respectively. OXM and GLU stimulated cyclic AMP levels with relative ED50 of approx. 1 and 30, respectively, whereas OXM (19-37) was totally ineffective on this parameter. In contrast to carbachol, none of the peptides significantly modified the inositol phosphate turnover or induced rapid changes in cellular free Ca2+. We conclude that the RIN T3 cells contain a receptor-cyclic AMP system similar to that found in gastric mucosa and that this system is linked to somatostatin release. Another receptor-second messenger mechanism linked to somatostatin release is triggered by the (19-37) fragment. This mechanism is not the inositol phosphate/Ca2+ cascade triggered in the same cells by cholinergic agents.
Insights
Oxyntomodulin (OXM) and glucagon stimulate somatostatin release and cyclic AMP in RIN T3 cells. A separate pathway involving the OXM (19-37) fragment also triggers somatostatin release.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Pharmacology
Background:
- Somatostatin plays a crucial role in regulating gastric acid secretion and other physiological processes.
- RIN T3 cells are a well-established model for studying pancreatic islet cell function and hormone secretion.
Purpose of the Study:
- To investigate the effects of oxyntomodulin (OXM), its C-terminal fragment (OXM (19-37)), and glucagon (GLU) on somatostatin release in RIN T3 cells.
- To elucidate the signaling pathways involved, including cyclic AMP accumulation, inositol phosphate turnover, and intracellular calcium changes.
- To compare the actions of these peptides with carbachol, a known activator of the inositol phosphate/Ca2+ cascade.
Main Methods:
- Cultured RIN T3 cells were treated with OXM, OXM (19-37), GLU, and carbachol.
- Somatostatin release was measured.
- Cyclic AMP accumulation was assessed.
- Inositol phosphate turnover and intracellular free Ca2+ levels were monitored using fura-2.
Main Results:
- OXM, GLU, and OXM (19-37) all stimulated somatostatin release, with OXM being the most potent.
- OXM and GLU increased cyclic AMP levels, while OXM (19-37) had no effect.
- None of the tested peptides affected inositol phosphate turnover or induced rapid changes in intracellular Ca2+, unlike carbachol.
Conclusions:
- RIN T3 cells possess a receptor-cyclic AMP system linked to somatostatin release, similar to that in gastric mucosa.
- A distinct receptor-second messenger mechanism, not involving the inositol phosphate/Ca2+ cascade, mediates somatostatin release stimulated by the OXM (19-37) fragment.