Atkins, Annette R.

Over the last decades, epidemiology and functional studies have started to reveal a pivotal role of vitamin D in both type 1 and type 2 diabetes pathogenesis. Acting through the vitamin D receptor (VDR), vitamin D regulates insulin secretion in pancreatic islets and insulin sensitivity in multiple peripheral metabolic organs. In vitro studies and both T1D and T2D animal models showed that vitamin D can improve glucose homeostasis by enhancing insulin secretion, reducing inflammation, reducing autoimmunity, preserving beta cell mass, and sensitizing insulin action. Conversely, vitamin D deficiency has been shown relevant in increasing T1D and T2D incidence. While clinical trials testing the hypothesis that vitamin D improves glycemia in T2D have shown conflicting results, subgroup and meta-analyses support the idea that raising serum vitamin D levels may reduce the progression from prediabetes to T2D. In this review, we summarize current knowledge on the molecular mechanisms of vitamin D in insulin secretion, insulin sensitivity, and immunity, as well as the observational and interventional human studies investigating the use of vitamin D as a treatment for diabetes.

Significance Glucocorticoids are widely prescribed antiinflammatory drugs that suppress inflammatory gene expression through activation of the glucocorticoid receptor (GR); however, the mechanisms of GR-mediated repression are not fully understood. We show here that bromodomain containing 9 (BRD9), a component of the SWI/SNF chromatin remodeling complex, modulates GR activity in bone marrow-derived macrophages. Loss of BRD9 activity in macrophages attenuated the response to liposaccharides and interferon inflammatory stimuli. Notably, BRD9 inhibition synergized with the synthetic glucocorticoid dexamethasone to suppress the inflammatory response in macrophages. Our data support a model in which BRD9 restricts GR binding at a subset of inflammatory related genes, and suggests that BRD9 inhibitors may increase the efficacy of glucocorticoids.