Effects of peripherally administered urocortin 3 on feeding behavior and gastric emptying in mice

Terashi, Mutsumi; Asakawa, Akihiro; Cheng, Kai‐Chun; Koyama, Ken; Chaolu, Huke; Ushikai, Miharu; Inui, Akio

doi:10.3892/etm.2011.200

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…Our finding that Ucn3 treatment significantly prevented body weight gain during colitis can be explained by previous studies that show Ucn3 decreases food intake [43] and gastric emptying [29] and/or due to its natriuretic action under stress [35]. In our study, Ucn3 did not ameliorate or exacerbate inflammation as assessed by histopathology and changes in inflammatory cytokines such as TNF-α and IL-6; nonetheless, the significant effect of Ucn3 on thymus weight suggests the presence of some important actions of Ucn3 on thymus-related immunity, which needs further investigations.…”

Section: Discussionsupporting

confidence: 60%

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Urocortin 3 expression at baseline and during inflammation in the colon: Corticotropin releasing factor receptors cross-talk

et al. 2014

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Urocortins (Ucn1–3), members of the corticotropin-releasing factor (CRF) family of neuropeptides, are emerging as potent immunomodulators. Localized, cellular expression of Ucn1 and Ucn2, but not Ucn3, has been demonstrated during inflammation. Here, we investigated the role of Ucn3 in a rat model of Crohn’s colitis and the relative contribution of CRF receptors (CRF1 and CRF2) in regulating Ucn3 expression at baseline and during inflammation. Ucn3 mRNA and peptide were ubiquitously expressed throughout the GI tract in naïve rats. Ucn3 immunoreactivity was seen in epithelial cells and myenteric neurons. On day 1 of colitis, Ucn3 mRNA levels decreased by 80% and did not recover to baseline even by day 9. Next, we ascertained pro- or anti-inflammatory actions of Ucn3 during colitis. Surprisingly, unlike observed anti-inflammatory actions of Ucn1, exogenous Ucn3 did not alter histopathological outcomes during colitis and neither did it alter levels of pro-inflammatory cytokines IL-6 and TNF-α. At baseline, colon-specific knockdown of CRF1, but not CRF2 decreased Ucn3 mRNA by 78%, whereas during colitis, Ucn3 mRNA levels increased after CRF1 knockdown. In cultured cells, co-expression of CRF1 + CRF2 attenuated Ucn3-stimulated intracellular Ca2+ peak by 48% as compared to cells expressing CRF2 alone. Phosphorylation of p38 kinase increased by 250% during colitis and was significantly attenuated after Ucn3 administration. Thus, our results suggest that a balanced and coordinated expression of CRF receptors is required for proper regulation of Ucn3 at baseline and during inflammation.

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Section: Discussionsupporting

confidence: 60%

“…Central actions of Ucn3 include decrease in ethanol and food intake [40]. Peripheral actions also inhibit feeding behavior and delay gastric emptying in a dose-dependent manner [29,43]. …”

Section: Introductionmentioning

confidence: 99%

Urocortin 3 expression at baseline and during inflammation in the colon: Corticotropin releasing factor receptors cross-talk

et al. 2014

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“…In our first in vivo study, blood glucose concentrations in rats receiving glucose orally and either saline (control group) or UCN3 subcutaneously were similar, apparently indicating that UCN3 did not affect intestinal glucose entry, absorption, or disposal. However, this was clearly not the case since both gastric emptying and glucose absorption and insulin secretion were reduced by >50%, in agreement with previous findings in mice and rats [ 14 , 15 ]. Here, we show that the maximal efficacy of UCN3 was comparable with that of GLP-1 but that the effect was more sustained, possibly because of a longer t½ of UCN3.…”

Section: Discussionsupporting

confidence: 90%

Opposing roles of the entero-pancreatic hormone urocortin-3 in glucose metabolism in rats

et al. 2022

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Aim/hypothesis Urocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved. Methods We studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats. To supplement these physiological studies, we mapped the expression of UCN3 and the UCN3-sensitive receptor, type 2 corticotropin-releasing factor receptor (CRHR2), by means of fluorescence in situ hybridisation and by gene expression analysis. Results In rats, s.c. administration of UCN3 strongly inhibited gastric emptying and glucose absorption after oral administration of glucose. Direct inhibition of gastrointestinal motility may be responsible because UCN3’s cognate receptor, CRHR2, was detected in gastric submucosal plexus and in interstitial cells of Cajal. Despite inhibited glucose absorption, post-challenge blood glucose levels matched those of rats given vehicle in the low-dose UCN3 group, because UCN3 concomitantly inhibited insulin secretion. Higher UCN3 doses did not further inhibit gastric emptying, but the insulin inhibition progressed resulting in elevated post-challenge glucose and lipolysis. Incretin hormones and somatostatin (SST) secretion from isolated perfused rat small intestine was unaffected by UCN3 infusion; however, UCN3 infusion stimulated secretion of somatostatin from delta cells in the isolated perfused rat pancreas which, unlike alpha cells and beta cells, expressed Crhr2. Conversely, acute antagonism of CRHR2 signalling increased insulin secretion by reducing SST signalling. Consistent with these observations, acute drug-induced inhibition of CRHR2 signalling improved glucose tolerance in rats to a similar degree as administration of glucagon-like peptide-1. UCN3 also powerfully inhibited glucagon secretion from isolated perfused rat pancreas (perfused with 3.5 mmol/l glucose) in a SST-dependent manner, suggesting that UCN3 may be involved in glucose-induced inhibition of glucagon secretion. Conclusions/interpretation Our combined data indicate that UCN3 is an important glucoregulatory hormone that acts through regulation of gastrointestinal and pancreatic functions. Graphical abstract

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“…In both light and dark phases, IP administration of UCN3 suppresses food intake in mice. Food intake and body weight gain are inhibited by long-term UCN3 administration (57,64,73). The feeding-inhibitory action of IP administered UCN3 is the weakest of the CRF family peptides (57).…”

Section: Ucn3mentioning

confidence: 99%

The role of CRF family peptides in the regulation of food intake and anxiety-like behavior

Nakayama

Suzuki

et al. 2011

BioMolecular Concepts

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Corticotropin-releasing factor (CRF) and the urocortins (UCN1, UCN2, and UCN3) belong to the CRF family of peptides and are the major regulators of the adaptive response to internal and external stresses. The actions of CRF and UCNs are mediated through two receptor subtypes: CRF receptor 1 (CRFR1) and CRFR2. Their physiological roles, among other functions, include the regulation of food intake and anxiety-like behavior. In this review, we describe the progress that has been made towards understanding how anxiety-and depression-like behavior and food intake are regulated by CRF, UCN1, UCN2, and UCN3.

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Effects of peripherally administered urocortin 3 on feeding behavior and gastric emptying in mice

Cited by 8 publications

References 23 publications

Urocortin 3 expression at baseline and during inflammation in the colon: Corticotropin releasing factor receptors cross-talk

Urocortin 3 expression at baseline and during inflammation in the colon: Corticotropin releasing factor receptors cross-talk

Opposing roles of the entero-pancreatic hormone urocortin-3 in glucose metabolism in rats

The role of CRF family peptides in the regulation of food intake and anxiety-like behavior

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