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

• Published in: Islets 2017-11, Vol.9 (6), p.150-158
• Main Authors: Pasek, Raymond C., Dunn, Jennifer C., Elsakr, Joseph M., Aramandla, Mounika, Matta, Anveetha R., Gannon, Maureen
• Format: Article
• Language: English
• Subjects: 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; gestational diabetes; Haploinsufficiency; Heterozygote; Immunohistochemistry; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; islets; Loss of Function Mutation; Mice, Inbred C57BL; Mice, Transgenic; pancreas; Pancreas - blood supply; Pancreas - metabolism; Pancreas - pathology; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Pregnancy; Research Paper; Up-Regulation; β cell proliferation
• ISSN: 1938-2014; 1938-2022
• DOI: 10.1080/19382014.2017.1356963

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 (Ctgf LacZ/+ ) have an impairment in maternal β cell proliferation, while β cell proliferation in virgin Ctgf LacZ/+ females is unaffected. Additionally, α-cell proliferation, β cell size, and GSIS were unaffected in Ctgf LacZ/+ mice, suggesting that vascular-derived Ctgf has a specific role in islet compensation during pregnancy.