Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital

Novel GLP-1/GLP-2 co-agonists display marked effects on gut volume and improves glycemic control in mice

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Post-oral fat-induced satiation is mediated by endogenous CCK and GLP-1 in a fat self-administration mouse model

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Association between habitual sleep duration/quality and appetite markers in individuals with obesity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Decreased spontaneous activity in AMPK α2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Pernille Wismann
  • Søren L Pedersen
  • Gitte Hansen
  • Karin Mannerstedt
  • Philip J Pedersen
  • Palle B Jeppesen
  • Niels Vrang
  • Keld Fosgerau
  • Jacob Jelsing
Vis graf over relationer

AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies.

METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice.

RESULTS: Sub-chronic administration of GUB09-123 to lean mice significantly reduced food intake, improved glucose tolerance, and increased gut volume, superior to monotherapy with the GLP-2 analogue teduglutide. Chronic administration of GUB09-123 to diabetic mice significantly improved glycemic control and showed persistent effects on gastric emptying, superior to monotherapy with the GLP-1 analogue liraglutide. Due to the short-acting nature of the molecule, no effects on body weight were observed, whereas a marked and robust intestinotrophic effect on mainly the small intestine volume and surface area was obtained. In contrast to GUB09-123, sub-chronic administration of a half-life extended GUB09-145 to lean mice caused marked dose-dependent effects on body weight while maintaining its potent intestinotrophic effect.

CONCLUSION: Our data demonstrate that the GLP-1/GLP-2 co-agonists have effects on gut morphometry, showing a marked increase in intestinal volume and mucosal surface area. Furthermore, effects on glucose tolerance and long-term glycemic control are evident. Effects on body weight and gastric emptying are also observed depending on the pharmacokinetic properties of the molecule. We suggest that this novel co-agonistic approach could exemplify a novel concept for treatment of T2DM or SBS.

TidsskriftPhysiology & Behavior
Sider (fra-til)72-81
Antal sider10
StatusUdgivet - 1 aug. 2018

ID: 56503220