Selective disruption of Tcf7l2 in the pancreatic β cell impairs secretory function and lowers β cell mass.
Bottom Line: Single nucleotide polymorphisms in the T-cell factor 7-like 2 (TCF7L2) gene, associated with T2D by genome-wide association studies, lead to impaired β cell function.Tcfl2(fl/fl)::Ins1Cre islets displayed defective glucose- and GLP-1-stimulated insulin secretion and the expression of both the Ins2 (∼20%) and Glp1r (∼40%) genes were significantly reduced.These data demonstrate that Tcf7l2 plays a cell autonomous role in the control of β cell function and mass, serving as an important regulator of gene expression and islet cell coordination.
Affiliation: Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine.Show MeSH
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Mentions: To determine whether alterations in β (or α) cell mass also might contribute to impaired insulin production in vivo after Tcf7l2 elimination, pancreata from 20-week-old Tcf7l2fl/fl::Ins1.Cre+mice that had been maintained on a HFD for 12 weeks were stained for insulin and glucagon, respectively, and analyzed by optical projection tomography (OPT). Cre+ islets displayed a markedly (31.7%, P < 0.05; n = 4 mice per genotype) decreased β cell mass, but normal α-cell mass, compared with littermate controls (Fig. 4), resulting in an overall decrease in β to α cell ratio. The number of smaller insulin-stained islets was particularly sharply decreased in TCF7L2fl/fl::Ins1.Cre+ mouse islets (Fig. 4B).Figure 4.
Affiliation: Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine.