Sustained expression of the transcription factor GLIS3 is required for normal beta cell function in adults.
Bottom Line: Genome-wide association studies identified GLIS3 as a susceptibility locus for type 1 and type 2 diabetes.GLIS3 controls beta cell proliferation in response to high-fat feeding at least partly by regulating Ccnd2 transcription.We conclude that normal Glis3 expression is required for pancreatic beta cell function and mass maintenance during adulthood, which impairment leads to diabetes in adults.
Affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Diabetes and Endocrinology Research Center, Baylor College of Medicine, Houston, TX, USA.Show MeSH
Related in: MedlinePlus
Mentions: The neonatal lethality in Glis3−/− mice (Kang et al, 2009; Watanabe et al, 2009; Yang et al, 2011) prevents us from investigating the role of homozygous loss of Glis3 in the adult pancreas in these mice. We, therefore, examined Glis3's function in heterozygotes. Glis3+/− and Glis3+/+ mice exhibited similar body weights whether they were put on a regular chow diet (CD) or a HFD for 20 weeks (Fig 1A and B). While on a CD for 20 weeks, Glis3+/− and Glis3+/+ mice displayed similar fasting blood glucose, glucose tolerance (Fig 1C) and plasma insulin during glucose tolerance test (GTT; Fig 1D), although the Glis3+/− showed a trend towards higher plasma glucose compared to Glis3+/+ controls after glucose challenge (Fig 1C). However, after HFD feeding for 20 weeks, Glis3+/− mice developed diabetes with significantly higher fasting blood glucose (Fig 1E). They also displayed increased blood glucose but lower plasma insulin levels during GTT (Fig 1F), as compared to Glis3+/+ controls, indicating severe pancreatic beta cell dysfunction in adult Glis3+/− mice in response to HFD feeding.
Affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Diabetes and Endocrinology Research Center, Baylor College of Medicine, Houston, TX, USA.