Inhibition of Insulin Release by Urotensin II - A Study on the Perfused Rat Pancreas

Ra, Silvestre; Rodriguez-Gallardo, J.; Em, Egido; Marco, José

doi:10.1055/s-2001-15414

Cited by 65 publications

(54 citation statements)

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“…We have previously reported that frog UII, at a high concentration (100 nmol/l), attenuates glucoseinduced insulin secretion in the perfused rat pancreas (30). We now show that, in this model, rat UII inhibits insulin secretion, in a concentration-dependent manner, with an IC 50 of 0.12 nmol/l.…”

Section: Discussionmentioning

confidence: 50%

“…Interestingly, it has recently been shown that the UII gene has a role in genetic susceptibility to type 2 diabetes mellitus in Chinese (28) and Japanese (29) subjects. On the other hand, we have previously reported that, in the rat pancreas, frog UII at a high concentration (100 nmol/l) inhibits glucose-and arginine-induced insulin responses (30). Taken together, these observations suggest a role for UII in the pathogenesis of diabetes mellitus.…”

Section: Introductionmentioning

confidence: 54%

“…However, no changes either in the perfusate flow rate or in the pressure of the perfusion system were observed during UII infusion. An effect to selectively reduce the perfusate supply to the islets could not only reduce insulin output but could also affect the overall islet secretion and, as described in our previous work (30), UII infusion did not modify glucagon or somatostatin output. Furthermore, in the herein reported experiments UII did not affect basal insulin release, thus excluding vasoconstriction as a factor hampering the secretory activity of the pancreatic islet.…”

Section: Discussionmentioning

confidence: 80%

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Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

Silvestre

Egido

Hernández

et al. 2004

European Journal of Endocrinology

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Objective: Previous work from our laboratory has demonstrated that frog urotensin-II (UII), at a high concentration, inhibits glucose-induced insulin release in the rat pancreas. We have investigated the effect of rat UII and two structural analogs on insulin secretion and searched for the presence of UII-immunoreactivity in rat pancreatic extracts. Methods: The study was performed in the perfused rat pancreas. UII as well as its analogs were synthesized by solid phase methodology. Pancreatic extracts were analyzed for UII by reversed-phase HPLC combined with a sensitive UII RIA. Results: Infusion of synthetic rat UII inhibited glucose-induced insulin release in a dose-dependent manner (IC 50 : 0.12 nmol/l). UII (1 nmol/l) also inhibited the insulin responses induced by carbachol, glucagon-like peptide-1, and a calcium channel agonist (BAY K 8644). The inhibitory effect of UII was mimicked by the potent G protein-coupled receptor (GPR14) agonist [3-iodo-Tyr 6 ]UII(4 -11). In contrast, [Ala 8 ]UII(4 -11), a UII analog devoid of contractile activity on rat aortic rings, did not affect glucose-induced insulin secretion. Analysis of rat pancreatic extracts revealed the presence of an immunoreactive peptide exhibiting the same retention time as synthetic rat UII.Conclusions: Our results demonstrate that UII is a potent insulinostatic peptide. The observation that UII is actually present in the pancreas suggests that this peptide may play a physiological role in the control of insulin secretion. Concerning the two UII analogs tested, only ]UII(4 -11), reportedly possessing GPR14-mediated contractile activity, mimics the insulinostatic effect of UII. This finding would support the view that UII acts on the pancreatic beta cell through the GPR14 receptor.European Journal of Endocrinology 151 803-809

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Section: Discussionmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 80%

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Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

Silvestre

Egido

Hernández

et al. 2004

European Journal of Endocrinology

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“…Both the stimulation of corticosterone production and the absence of effects have been reported in the amphibians marsh frog (Pelophylax ridibundus) and axolotl (Ambystoma mexicanum; Feuilloley et al 1994, Gupta & Hanke 1994. Metabolic effects have also been described, including the inhibition of insulin's response to glucose in isolated rat perfused pancreas with no effect on glucagon and SS1 release (Silvestre et al 2001, Marco et al 2008). This suggests a direct effect on b-cells.…”

Section: Uts2r5mentioning

confidence: 93%

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Tostivint¹,

Daza²,

Bergqvist³

et al. 2014

Journal of Molecular Endocrinology

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Somatostatin (SS) and urotensin II (UII) are members of two families of structurally related neuropeptides present in all vertebrates. They exert a large array of biological activities that are mediated by two families of G-protein-coupled receptors called SSTR and UTS2R respectively. It is proposed that the two families of peptides as well as those of their receptors probably derive from a single ancestral ligand-receptor pair. This pair had already been duplicated before the emergence of vertebrates to generate one SS peptide with two receptors and one UII peptide with one receptor. Thereafter, each family expanded in the three whole-genome duplications (1R, 2R, and 3R) that occurred during the evolution of vertebrates, whereupon some local duplications and gene losses occurred. Following the 2R event, the vertebrate ancestor is deduced to have possessed three SS (SS1, SS2, and SS5) and six SSTR (SSTR1-6) genes, on the one hand, and four UII (UII, URP, URP1, and URP2) and five UTS2R (UTS2R1-5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception of SSTR4. Moreover, several additional genes have been gained through the 3R event, such as SS4 and a second copy of the UII, SSTR2, SSTR3, and SSTR5 genes, and through local duplications, such as SS3. In mammals, all the genes of the SSTR family have been preserved, with the exception of SSTR6. In contrast, for the other families, extensive gene losses occurred, as only the SS1, SS2, UII, and URP genes and one UTS2R gene are still present.

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“…However, UII showed no significant effect on the mRNA expression of both Igf1 and Igf2 at any dose or any time point (Supplementary Figure 3, see section on supplementary data given at the end of this article), which indicates that UII cannot exert a direct effect on igf1 and igf2 gene transcription. Because, in addition to GH, other hormones, such as insulin, SS, cortisol, and thyroid hormones, can also influence igf mRNA expression in the liver and extrahepatic tissues (Reindl & Sheridan 2012) and UII is known to regulate the secretion of various hormones, such as prolactin, TSH (Gartlon et al 2001), and insulin (Silvestre et al 2001), we cannot exclude the possibility that UII indirectly stimulates igf mRNA expression through the regulation of other hormones in the liver. Collectively, these results delineate the hypothetical regulation of the transcription of genes encoding major hormones controlling growth in grouper by UII: after the i.p.…”

Section: Discussionmentioning

confidence: 94%

UII and UT in grouper: cloning and effects on the transcription of hormones related to growth control

Sun

Duan

et al. 2013

Journal of Endocrinology

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Urotensin II (UII) is a cyclic peptide that was originally extracted from the caudal neurosecretory system (CNSS) of fish. UII is well known to exhibit cardiovascular, ventilatory, and motor effects in vertebrates. Studies have reported that UII exerts mitogenic effects and can act as an autocrine/paracrine growth factor in mammals. However, similar information in fish is limited. In this study, the full-length cDNAs of UII and its receptor (UT) were cloned and characterized in the orange-spotted grouper. UII and UT were expressed ubiquitously in various tissues in grouper, and particularly high levels were observed in the CNSS, CNS, and ovary. A functional study showed that UT was coupled with intracellular Ca 2C mobilization in HEK293 cells. Studies carried out using i.p. injections of UII in grouper showed the following: i) in the hypothalamus, UII can significantly stimulate the mRNA expression of ghrh and simultaneously inhibit the mRNA expression of somatostatin 1 (ss1) and ss2 3 h after injection; ii) in the pituitary, UII also significantly induced the mRNA expression of gh 6 and 12 h after injection; and iii) in the liver, the mRNA expression levels of ghr1/ghr2 and igf1/igf2 were markedly increased 12 and 3 h after the i.p. injection of UII respectively. These results collectively indicate that the UII/UT system may play a role in the promotion of the growth of the orange-spotted grouper.

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Inhibition of Insulin Release by Urotensin II - A Study on the Perfused Rat Pancreas

Cited by 65 publications

References 9 publications

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

UII and UT in grouper: cloning and effects on the transcription of hormones related to growth control

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