Incretin receptor null mice reveal key role of GLP-1 but not GIP in pancreatic beta cell adaptation to pregnancy

PLoS One. 2014 Jun 13;9(6):e96863. doi: 10.1371/journal.pone.0096863. eCollection 2014.


Islet adaptations to pregnancy were explored in C57BL6/J mice lacking functional receptors for glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). Pregnant wild type mice and GIPRKO mice exhibited marked increases in islet and beta cell area, numbers of medium/large sized islets, with positive effects on Ki67/Tunel ratio favouring beta cell growth and enhanced pancreatic insulin content. Alpha cell area and glucagon content were unchanged but prohormone convertases PC2 and PC1/3 together with significant amounts of GLP-1 and GIP were detected in alpha cells. Knockout of GLP-1R abolished these islet adaptations and paradoxically decreased pancreatic insulin, GLP-1 and GIP. This was associated with abolition of normal pregnancy-induced increases in plasma GIP, L-cell numbers, and intestinal GIP and GLP-1 stores. These data indicate that GLP-1 but not GIP is a key mediator of beta cell mass expansion and related adaptations in pregnancy, triggered in part by generation of intra-islet GLP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Size
  • Female
  • Gastric Inhibitory Polypeptide / blood
  • Gene Knockout Techniques
  • Glucagon-Like Peptide 1 / blood*
  • Glucagon-Like Peptide-1 Receptor
  • Insulin / metabolism*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy / metabolism*
  • Receptors, Gastrointestinal Hormone / genetics*
  • Receptors, Gastrointestinal Hormone / metabolism
  • Receptors, Glucagon / genetics*
  • Receptors, Glucagon / metabolism


  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Insulin
  • Receptors, Gastrointestinal Hormone
  • Receptors, Glucagon
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • gastric inhibitory polypeptide receptor