Effect of GIP, GLP-1, insulin and gastrin on ghrelin release in the isolated rat stomach

Lippl, Florian; Kircher, F.; Erdmann, Johannes; Allescher, Hans–Dieter; Schusdziarra, V.

doi:10.1016/j.regpep.2004.01.003

Cited by 95 publications

(84 citation statements)

References 45 publications

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“…An inverse relationship between GLP-1 and ghrelin levels has been demonstrated after a standard glucose tolerance test in humans (17). Furthermore, GLP-1 was shown to reduce the levels of ghrelin paradoxically elevated by vagal stimulation in vitro (18). Together, these findings suggest that GLP-1 or related peptides might be involved in regulating ghrelin.…”

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confidence: 79%

Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats

et al. 2007

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Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia appears to promote an increase in food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor (GLP-1r) that has anorexigenic and fat-reducing properties. Here, we report that Ex-4 reduces the levels of ghrelin by up to 74% in fasted rats. These effects are dose dependent and long lasting (up to 8 h), and they can be detected after both central and peripheral administration of Ex-4. Suppression of ghrelin was neither mimicked by GLP-1(7-36)-NH 2 nor blocked by the GLP-1r antagonist Ex-(9 -39). Moreover, it was independent of the levels of leptin and insulin. The decrease in ghrelin levels induced by Ex-4 may explain the reduced food intake in fasted rats, justifying the more potent anorexigenic effects of Ex-4 when compared with GLP-1. As well as the potential benefits of Ex-4 in type 2 diabetes, the potent effects of Ex-4 on ghrelin make it tempting to speculate that Ex-4 could offer a therapeutic option for PWS and other syndromes characterized by substantial amounts of circulating ghrelin. Diabetes 56: 143-151, 2007

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confidence: 79%

Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats

et al. 2007

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“…The predominant expression of sst 5 receptors on b-cells is the histological correlate for the 11-foldstronger inhibitory effect of SOM230 on insulin secretion compared with octreotide (25). Several studies have shown that circulating insulin has an inhibitory effect on ghrelin secretion (33)(34)(35). Therefore, by inhibiting insulin secretion via the activation of sst 5 receptors in the pancreas, SOM230 at 10 mg/kg could disinhibit the inhibitory effect of insulin on ghrelin secretion, leading to a further increase in ghrelin.…”

Section: Discussionmentioning

confidence: 99%

Regulation of ghrelin secretion by somatostatin analogs in rats

Silva¹,

Bethmann²,

Raulf³

et al. 2005

eur j endocrinol

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Objective: Ghrelin is a hormone present in the plasma in two forms: octanoylated and des-octanoylated ghrelin. In pathophysiological conditions such as Prader -Willi syndrome and ghrelinoma, elevated ghrelin plasma levels are associated with pathological obesity. Clinical studies have shown that somatostatin downregulates ghrelin plasma levels in healthy volunteers. The aim of this study was to investigate the effects of two somatostatin analogues, SOM230 and octreotide, on ghrelin secretion in rats. Methods: Ghrelin secretion was either unstimulated or stimulated by overnight fasting. Treatment with SOM230 and octreotide was either acute (s.c. injection 1 h before blood sampling) or prolonged (continuous s.c. infusion via 14-day osmotic minipumps). Results: Acute treatment with octreotide dose-dependently inhibited unstimulated and stimulated secretion of total and active ghrelin. SOM230 (30 mg/kg) inhibited active ghrelin in fasted rats. Lower doses had no effect. After 7 days of treatment, active ghrelin was strongly inhibited by both compounds in fasted animals, with a stronger effect for octreotide. Lower inhibition was achieved in fed rats. After 14 days, the inhibition with octreotide in fasted rats was lower and SOM230 had no effect. Somatostatin receptor expression analysis in the rat glandular stomach revealed a predominant sst 1 and sst 2 expression, low expression of sst 3 and sst 4 , and hardly detectable sst 5 mRNA expression. Conclusions: Somatostatin analogues may be useful for the inhibition of physiologically elevated ghrelin plasma levels. This inhibition appears to be mediated by sst 2 receptors in the rat, and desensitizes after 14 days of treatment.European Journal of Endocrinology 152 887-894

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“…The peptides of the CCK -gastrin family have also indirect actions via the secretion of other regulatory substances. As an example, it was recently suggested that gastrin is a potential candidate for the postprandial decrease of ghrelin secretion in the rat (Lippl et al 2004).…”

Section: Physiological Effects Of Gastrin and Cholecystokininmentioning

confidence: 99%

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

et al. 2006

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The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK 1 and CCK 2 receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.

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Effect of GIP, GLP-1, insulin and gastrin on ghrelin release in the isolated rat stomach

Cited by 95 publications

References 45 publications

Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats

Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats

Regulation of ghrelin secretion by somatostatin analogs in rats

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

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