Transient Dexamethasone Loading Induces Prolonged Hyperglycemia in Male Mice with Histone Acetylation in Dpp-4 Promoter

Endocrinology. 2021 Sep 4:bqab193. doi: 10.1210/endocr/bqab193. Online ahead of print.ABSTRACTGlucocorticoid causes hyperglycemia which is common in patients with or without diabetes. We experience prolonged hyperglycemia even after the discontinuation of glucocorticoid use. In the present study, we examined time course of blood glucose level in the patients of our hospital who received transient glucocorticoid treatment. In addition, the mechanism of prolonged hyperglycemia was investigated by using dexamethasone (Dexa)-treated mice and cultured cells. The blood glucose level in glucose tolerance test, level of insulin and glucagon-like peptide 1 (GLP-1) and the activity of dipeptidyl peptidase 4 (DPP-4) were examined during and after Dexa-loading in mice, with histone acetylation level of the promoter region. Mice showed prolonged hyperglycemia during and after transient Dexa-loading accompanied by persistently lower blood GLP-1 level and higher activity of DPP-4. The expression level of Dpp-4 was increased in the mononuclear cells and the promoter region of Dpp-4 was hyperacetylated during and after the transient Dexa treatment. In vitro experiments also indicated development of histone hyperacetylation in the Dpp-4 promoter region during and after Dexa treatment. The upregulation of Dpp-4 in cultured cells was significantly inhibited by a histone acetyltransferase inhibitor. Moreover, the histone hyperacetylation induced by Dexa was reversible by the treatment with a sirt...
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research