Connective tissue growth factor is critical for proper β-cell function and pregnancy-induced β-cell hyperplasia in adult mice

Am J Physiol Endocrinol Metab. 2016 Sep 1;311(3):E564-74. doi: 10.1152/ajpendo.00194.2016. Epub 2016 Jul 26.

Abstract

During pregnancy, maternal β-cells undergo compensatory changes, including increased β-cell mass and enhanced glucose-stimulated insulin secretion. Failure of these adaptations to occur results 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 adult pancreas, CTGF is expressed only in the vasculature. Here we show that pregnant mice with global Ctgf haploinsufficiency (Ctgf(LacZ/+)) have an impairment in maternal β-cell proliferation; no difference was observed in virgin Ctgf(LacZ/+) females. Using a conditional CTGF allele, we found that mice with a specific inactivation of CTGF in endocrine cells (Ctgf(ΔEndo)) develop gestational diabetes during pregnancy, but this is due to a reduction in glucose-stimulated insulin secretion rather than impaired maternal β-cell proliferation. Moreover, virgin Ctgf(ΔEndo) females also display impaired GSIS with glucose intolerance, indicating that underlying β-cell dysfunction precedes the development of gestational diabetes in this animal model. This is the first time a role for CTGF in β-cell function has been reported.

Keywords: gestational diabetes mellitus; islet function; β-cell proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • Aging
  • Alleles
  • Animals
  • Cell Size*
  • Connective Tissue Growth Factor / deficiency
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism*
  • Diabetes, Gestational / metabolism
  • Diabetes, Gestational / physiopathology*
  • Disease Models, Animal
  • Embryonic Development
  • Endocrine Cells / metabolism
  • Endocrine Cells / physiology
  • Female
  • Glucose / pharmacology
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / ultrastructure
  • Islets of Langerhans / blood supply
  • Mice
  • Mice, Knockout
  • Pregnancy

Substances

  • CCN2 protein, mouse
  • Insulin
  • Connective Tissue Growth Factor
  • Glucose