Incretin Receptor Null Mice Reveal Key Role of GLP-1 but Not GIP in Pancreatic Beta Cell Adaptation to Pregnancy.

RC Moffett, Srividya Vasu, B Thorens, DJ Drucker, Peter Flatt

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pagese96863
JournalPLoS ONE
Volume9
DOIs
Publication statusPublished - 13 Jun 2014

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Gastric Inhibitory Polypeptide
Incretins
Glucagon-Like Peptide 1
Insulin-Secreting Cells
Pregnancy
Proprotein Convertase 2
Cell Count
Enteroendocrine Cells
Insulin
Glucagon
Islets of Langerhans
Growth

Cite this

Moffett, RC ; Vasu, Srividya ; Thorens, B ; Drucker, DJ ; Flatt, Peter. / Incretin Receptor Null Mice Reveal Key Role of GLP-1 but Not GIP in Pancreatic Beta Cell Adaptation to Pregnancy. In: PLoS ONE. 2014 ; Vol. 9. pp. e96863.
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abstract = "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.",
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Incretin Receptor Null Mice Reveal Key Role of GLP-1 but Not GIP in Pancreatic Beta Cell Adaptation to Pregnancy. / Moffett, RC; Vasu, Srividya; Thorens, B; Drucker, DJ; Flatt, Peter.

In: PLoS ONE, Vol. 9, 13.06.2014, p. e96863.

Research output: Contribution to journalArticle

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