Vascular-derived connective tissue growth factor (Ctgf) is critical for pregnancy-induced β cell hyperplasia in adult mice

Islets. 2017 Nov 2;9(6):150-158. doi: 10.1080/19382014.2017.1356963. Epub 2017 Nov 7.

Abstract

During pregnancy, maternal β cells undergo compensatory changes including hypertrophy, hyperplasia, and increased glucose-stimulated insulin secretion (GSIS). Failure of these adaptations to occur can result in gestational diabetes mellitus. The secreted protein, Connective tissue growth factor (Ctgf), is critical for normal β cell development and promotes regeneration after partial β cell ablation. During embryogenesis, Ctgf is expressed in pancreatic ducts, vasculature, and β cells. In the adult pancreas, Ctgf is expressed only in the vasculature. Here, we report that pregnant mice with global Ctgf haploinsufficiency (CtgfLacZ/+) have an impairment in maternal β cell proliferation, while β cell proliferation in virgin CtgfLacZ/+ females is unaffected. Additionally, α-cell proliferation, β cell size, and GSIS were unaffected in CtgfLacZ/+ mice, suggesting that vascular-derived Ctgf has a specific role in islet compensation during pregnancy.

Keywords: gestational diabetes; islets; pancreas; pregnancy; β cell proliferation.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Cell Proliferation
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism*
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / metabolism*
  • Diabetes, Gestational / pathology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Female
  • Genes, Reporter
  • Haploinsufficiency
  • Heterozygote
  • Immunohistochemistry
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Loss of Function Mutation
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pancreas / blood supply*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pregnancy
  • Up-Regulation

Substances

  • Blood Glucose
  • CCN2 protein, mouse
  • Insulin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Connective Tissue Growth Factor