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

• Published in: American journal of physiology: endocrinology and metabolism 2016-09, Vol.311 (3), p.E564-E574
• Main Authors: Pasek, Raymond C, Dunn, Jennifer C, Elsakr, Joseph M, Aramandla, Mounika, Matta, Anveetha R, Gannon, Maureen
• Format: Article
• Language: English
• Subjects: Aging; Alleles; Animals; Call for Papers; 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
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00194.2016

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.