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

Pasek RC, Dunn JC, Elsakr JM, Aramandla M, Matta AR, Gannon M
Am J Physiol Endocrinol Metab. 2016 311 (3): E564-74

PMID: 27460898 · PMCID: PMC5142004 · 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.

MeSH Terms (19)

Aging Alleles Animals Cell Size Connective Tissue Growth Factor Diabetes, Gestational Disease Models, Animal Embryonic Development Endocrine Cells Female Glucose Glucose Intolerance Glucose Tolerance Test Insulin Insulin-Secreting Cells Islets of Langerhans Mice Mice, Knockout Pregnancy

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