| Autor: |
Pasek RC; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;, Dunn JC; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;, Elsakr JM; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; and., Aramandla M; School for Science and Math, Vanderbilt University, Nashville, Tennessee., Matta AR; School for Science and Math, Vanderbilt University, Nashville, Tennessee., Gannon M; Department of Veterans Affairs Tennessee Valley, Nashville, Tennessee; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; and Maureen.gannon@vanderbilt.edu. |
| Abstrakt: |
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. |
