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

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 (CtgfLacZ/+) have an impairment in maternal β-cell proliferation; no difference was observed in virgin CtgfLacZ/+ females. Using a conditional CTGF allele, we found that mice with a specific inactivation of CTGF in endocrine cells (CtgfEndo) 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 CtgfEndo 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.

Source: AJP: Endocrinology and Metabolism - August 31, 2016 Category: Endocrinology Authors: Pasek, R. C., Dunn, J. C., Elsakr, J. M., Aramandla, M., Matta, A. R., Gannon, M. Tags: Call for Papers Source Type: research