Oxytocin is present in islets and plays a role in beta-cell function and survival

Mohan, Shruti; Khan, Dawood; Moffett, R. Charlotte; Irwin, Nigel; Flatt, Peter

doi:10.1016/j.peptides.2017.12.019

Cited by 34 publications

(35 citation statements)

References 54 publications

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“…This is encouraging given that type 2 diabetes is a disease characterised by beta-cell loss (Halban et al, 2014), although the exact mechanisms of these xenin-induced beneficial effects still needs to be elucidated. Similar to previous reports (Mohan et al, 2018;2019 (Irwin and Flatt, 2015;Craig et al, 2018). Furthermore, xenin has been suggested to supress food intake (Craig et al, 2018) and delay gastric emptying rate (Kim and Mizuno, 2010), which would also be complementary in the type 2 diabetes setting (Al-Goblan et al, 2014).…”

Section: Previous Reports Have Established That Chemical Manipulationsupporting

confidence: 93%

Effects of an enzymatically stable C-terminal hexapseudopeptide fragment peptide of xenin-25, ψ-xenin-6, on pancreatic islet function and metabolism

Craig

Gault

McClean

et al. 2019

Molecular and Cellular Endocrinology

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Xenin-25 undergoes rapid enzyme metabolism following secretion. Early studies demonstrated bioactivity of a C-terminal hexapeptide fragment of xenin-25, namely xenin-6, which were enhanced through introduction of a reduced N-terminal peptide bond, to yield Ψ-xenin-6. The present study was undertaken to define the biological actions and potential antidiabetic properties of Ψ-xenin-6. In vitro enzymatic stability, insulin and glucagon secretory activity, as well as effects on beta-cell survival were determined. Studies in mice were used to assess the impact of Ψ-xenin-6 on glucose homeostasis and satiety. Ψ-xenin-6 was resistant to murine plasma degradation. In BRIN-BD11 cells and isolated murine islets, Ψ-xenin-6 significantly stimulated insulin secretion, and prominently enhanced the insulinotropic actions of GIP. Xenin-6 and Ψ-xenin-6 had no impact on glucagon secretion, although xenin-6 partially reversed the glucagonotropic action of GIP. Further in vitro investigations revealed that, similar to GLP-1, Ψ-xenin-6 significantly augmented proliferation of human and rodent clonal betacells, whilst also fully protecting against cytokine-induced beta-cell cytotoxicity, with greater potency than xenin-25 and xenin-6. When administered to mice in combination with glucose, Ψ-xenin-6 significantly reduced glucose levels and enhanced glucose-induced insulin release, with a duration of biological action beyond 8 hours. Ψ-xenin-6 also significantly enhanced the glucose-lowering action of GIP in vivo. In overnight fasted mice, Ψ-xenin-6 exhibited satiety actions at both 25 and 250 nmol/kg. These data demonstrates that Ψ-xenin-6 is a metabolically stable C-terminal fragment analogue of xenin-25, with a metabolic action profile that merits further study as a potential antidiabetic compound.

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Section: Previous Reports Have Established That Chemical Manipulationsupporting

confidence: 93%

Effects of an enzymatically stable C-terminal hexapseudopeptide fragment peptide of xenin-25, ψ-xenin-6, on pancreatic islet function and metabolism

Craig

Gault

McClean

et al. 2019

Molecular and Cellular Endocrinology

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“…Amico and colleagues had shown that oxytocin is present in human pancreatic extracts which suggested the possibility of its local synthesis especially since OXT is noted to be an endocrine mediator for the release of insulin and glucagon [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

Oxytocin and oxytocin receptor alterations, decreased survival, and increased chemoresistance in patients with pancreatic cancer

Harricharran

Ogunwobi

2020

Hepatobiliary & Pancreatic Diseases International

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Background-Oxytocin (OXT) and its receptor (OXTR) is associated with cancer. The present study was to investigate the correlation between the genetic expression alterations of OXT and OXTR and the outcomes in patients with pancreatic cancer (PC). Methods-Information regarding OXT and OXTR genetic alterations and changes in gene expression were retrieved from the Cancer Genome Atlas (TCGA) databases and analyzed using the cBioPortal online tool. We assessed the correlation of overall survival and disease/progressionfree months to either OXT or OXTR genetic alterations and changes in gene expression using Kaplan-Meier and Cox regression analyses. Quantitative PCR (qPCR) was conducted to assess the mRNA expression levels of OXT and OXTR in human PC cell lines. Results-Five percent of PC cases showed mRNA upregulation in the OXT gene. These PC cases also showed genetic alterations and changes in gene expression of OXTR. The median *

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“…In support of this hypothesis, decreased insulin sensitivity and impaired glucose tolerance were found in oxytocin‐deficient ( Oxt −/− ) and high fat diet‐fed OTR‐deficient ( Oxtr −/− ) mice . In addition, peripheral oxytocin administration was shown to improve insulin sensitivity as well as glucose tolerance in mice maintained on standard and high‐fat diets, as well as in obese diabetic ( db/db ) mice . However, in a study conducted in obese ( ob/ob ) mice, 2 weeks of chronic treatment with oxytocin was associated with deteriorations in glucose and insulin tolerance.…”

Section: Cellular Mechanisms Of Oxytocin In Glucose Metabolismmentioning

confidence: 96%

“…The anorexigenic effect of oxytocin has been extensively documented in animals (12,52,80,82,83). However, definitive studies on the anorexigenic effects of oxytocin in humans are still lacking in light of discrepant results.…”

Section: Oxytocin System In Energy Balancementioning

confidence: 99%

Oxytocin in metabolic homeostasis: implications for obesity and diabetes management

2018

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Summary Oxytocin was once understood solely as a neuropeptide with a central role in social bonding, reproduction, parturition, lactation and appetite regulation. Recent evidence indicates that oxytocin enhances glucose uptake and lipid utilization in adipose tissue and skeletal muscle, suggesting that dysfunction of the oxytocin system could underlie the pathogenesis of insulin resistance and dyslipidaemia. Murine studies revealed that deficiencies in oxytocin signalling and oxytocin receptor expression lead to obesity despite normal food intake, motor activity and increased leptin levels. In addition, plasma oxytocin concentration is notably lower in obese individuals with diabetes, which may suggest an involvement of the oxytocin system in the pathogenesis of cardiometabolic disease. More recently, small scale studies demonstrated that intranasal administration of oxytocin was associated with significant weight loss as well as improvements in insulin sensitivity and pancreatic β‐cell responsivity in human subjects. The multi‐pronged effects of oxytocin signalling on improving peripheral insulin sensitivity, pancreatic function and lipid homeostasis strongly suggest a role for this system as a therapeutic target in obesity and diabetes management. The complexity of obesity aetiology and the pathogenesis of obesity‐related metabolic complications underscore the need for a systems approach to better understand the role of oxytocin in metabolic function.

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Oxytocin is present in islets and plays a role in beta-cell function and survival

Cited by 34 publications

References 54 publications

Effects of an enzymatically stable C-terminal hexapseudopeptide fragment peptide of xenin-25, ψ-xenin-6, on pancreatic islet function and metabolism

Effects of an enzymatically stable C-terminal hexapseudopeptide fragment peptide of xenin-25, ψ-xenin-6, on pancreatic islet function and metabolism

Oxytocin and oxytocin receptor alterations, decreased survival, and increased chemoresistance in patients with pancreatic cancer

Oxytocin in metabolic homeostasis: implications for obesity and diabetes management

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