title: Connective tissue growth factor is critical for proper β-cell function and pregnancy-induced β-cell hyperplasia in adult mice.
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.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Pasek
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Dunn
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; and.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Elsakr
authors.affiliation: School for Science and Math, Vanderbilt University, Nashville, Tennessee.
authors.forename: Mounika
authors.initials: M
authors.lastname: Aramandla
authors.affiliation: School for Science and Math, Vanderbilt University, Nashville, Tennessee.
authors.forename: Anveetha R
authors.initials: AR
authors.lastname: Matta
authors.affiliation: 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.
authors.forename: Maureen
authors.initials: M
authors.lastname: Gannon
mesh_terms: D000375:Aging; D000483:Alleles; D000818:Animals; D048429:Cell Size; D055513:Connective Tissue Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D047108:Embryonic Development; D055098:Endocrine Cells / Q000378:metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007515:Islets of Langerhans / Q000098:blood supply; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy
chemical_list: C526318:CCN2 protein, mouse; D007328:Insulin; D055513:Connective Tissue Growth Factor; D005947:Glucose
keywords: gestational diabetes mellitus; islet function; β-cell proliferation