Oxyntomodulin and its C-terminal octapeptide inhibit liquid meal-stimulated acid secretion

Jarrousse, C.; Niel, Huguette; Audousset-Puech, M. P.; Martinez, Jean; Bataille, D.

doi:10.1016/0196-9781(86)90196-8

Cited by 36 publications

(16 citation statements)

References 11 publications

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“…In support of this notion, GABA receptor agonists have been shown to suppress POMC biosynthesis in cultured neurointermediate lobes from the toad X. laevis [36]. A similar situation occurs in the rat intermediate lobe, where GABA exerts a direct inhibitory effect on POMC gene expression in melanotrope cells [37]. …”

Section: Discussionmentioning

confidence: 81%

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

et al. 2001

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The melanotrope population of the frog intermediate lobe consists of two subtypes of cells, referred to as high-(HD) and low-density (LD) melanotrope cells, which differ markedly in their basal morphofunctional features as well as their in vitro response to hypothalamic factors, such as the stimulator thyrotropin-releasing hormone (TRH) and the inhibitor dopamine. In this study, we have investigated whether other major hypothalamic regulators of the release of α-melanocyte-stimulating hormone (α-MSH), such as γ-aminobutyric acid (GABA) and neuropeptide Y (NPY), also differentially regulate frog melanotrope subpopulations. Our results show that in LD cells, both factors markedly inhibited proopiomelanocortin (POMC) mRNA accumulation and α-MSH secretion. In contrast, the secretory and biosynthetic activity of HD cells was not modified by GABA. NPY inhibited POMC transcript accumulation and tended to reduce α-MSH secretion in HD cells, yet these effects were less pronounced than those evoked in LD cells. In addition, GABA and NPY inhibited the KCl-induced rise in cytosolic free calcium levels in both subpopulations. Taken together, these results further indicate that frog melanotrope subpopulations are differentially regulated by the hypothalamus and strongly suggest that the intensity of such regulation is directly related to the activity of the cell subset. Thus, the LD subpopulation represents a highly responsive cell subset which is regulated by multiple neuroendocrine factors (TRH, dopamine, GABA and NPY), whereas the hormone storage HD subpopulation shows a moderate response to single stimulatory (TRH) and inhibitory (NPY) inputs.

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Section: Discussionmentioning

confidence: 81%

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

et al. 2001

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“…Although the physiological role of glicentin is not clearly established, oxyntomodulin has been shown to have an inhibitory effect on acid secretion by parietal cells from the stomach (12) and also to stimulate insulin secretion by pancreatic p-cells (13). However, these effects are observed at elevated, probably supraphysiological, concentrations of this hormone.…”

Section: Glp-imentioning

confidence: 99%

Glucagon-Like Peptide-I and the Control of Insulin Secretion in the Normal State and in NIDDM

1993

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Potentiation of glucose-induced insulin secretion by intestinal factors has been described for many years. Today, two major peptides with potent insulinotropic action have been recognized: gastric inhibitory peptide and truncated forms of glucagon-like peptide I, GLP-I(7-37) or the related GLP-I(7-36)amide. These hormones have specific beta-cell receptors that are coupled to production of cAMP and activation of cAMP-dependent protein kinase. Elevation in intracellular cAMP levels is required to mediate the glucoincretin effect of these hormones: the potentiation of insulin secretion in the presence of stimulatory concentrations of glucose. In addition, circulating glucoincretins maintain basal levels of cAMP, which are necessary to keep beta-cells in a glucose-competent state. Interactions between glucoincretin signaling and glucose-induced insulin secretion may result from the phosphorylation of key elements of the glucose signaling pathway by cAMP-dependent protein kinase. These include the ATP-dependent K+ channel, the Ca++ channel, or elements of the secretory machinery itself. In NIDDM, the glucoincretin effect is reduced. However, basal or stimulated gastric inhibitory peptide and glucagon-like peptide I levels are normal or even elevated, suggesting that signals induced by these hormones on the beta-cells are probably altered. At pharmacological doses, infusion of glucagon-like peptide I but not gastric inhibitory peptide, can ameliorate postprandial insulin secretory response in NIDDM patients. Agonists of the glucagon-like peptide I receptor have been proposed as new therapeutic agents in NIDDM.

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“…OXM potently inhibits gastric acid secretion and pancreatic enzyme secretion when infused iv (19,20). The C-terminal fragment of OXM, SP-1, has been described as the minimal active structure of OXM (21), as it has been found to mimic the actions of OXM in gastric mucosa, albeit less potently (19,22,23).…”

Section: P Reproglucagon Is Cleaved In a Tissue-specificmentioning

confidence: 99%

Oxyntomodulin Inhibits Food Intake in the Rat

et al. 2001

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Oxyntomodulin is derived from proglucagon processing in the intestine and the central nervous system. To date, no role in the central nervous system has been demonstrated. We report here that oxyntomodulin inhibits refeeding when injected intracerebroventricularly and into the hypothalamic paraventricular nucleus of 24-h fasted rats [intracerebroventricularly and into the paraventricular nucleus, 1 h, oxyntomodulin (1 nmol), 3.1 ؎ 0.5 g; saline, 6.2 ؎ 0.4 g; P < 0.005]. In addition, oxyntomodulin inhibits food intake in nonfasted rats injected at the onset of the dark phase (intracerebroventricularly, 1 h: oxyntomodulin, 3 nmol, 1.1 ؎ 0.19 g vs. saline, 2.3 ؎ 0.2 g; P < 0.05). This effect of oxyntomodulin on feeding is of a similar time course and magnitude as that of an equimolar dose of glucagon-like peptide-1. Other proglucagonderived products investigated [glucagon, glicentin (intracerebroventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol), and spacer peptide-1 (intracerebroventricularly and into the paraventricular nucleus, 3 nmol)] had no effect on feeding at any time point examined. The anorectic effect of oxyntomodulin (intracerebroventricularly, 3 nmol; into the paraventricular nucleus, 1 nmol) was blocked when it was coadministered with the glucagon-like peptide-1 receptor antagonist, exendin-(9 -39) (intracerebroventricularly, 100 nmol; into the paraventricular nucleus, 10 nmol). However, oxyntomodulin has a lower affinity for the glucagon-like peptide-1 receptor compared with glucagon-like peptide-1 (IC 50 : oxyntomodulin, 8.2 nM; glucagon-like peptide-1, 0.16 nM). One explanation for this is that there might be an oxyntomodulin receptor to which exendin-(9 -39) can also bind and act as an antagonist. (Endocrinology 142: 4244 -4250, 2001)

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Oxyntomodulin and its C-terminal octapeptide inhibit liquid meal-stimulated acid secretion

Cited by 36 publications

References 11 publications

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

Glucagon-Like Peptide-I and the Control of Insulin Secretion in the Normal State and in NIDDM

Oxyntomodulin Inhibits Food Intake in the Rat

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