Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

Hepatocyte Nuclear Factor 4-α (HNF4α) controls the insulin resistance-induced pancreatic β-cell mass expansion

2021; Elsevier BV; Volume: 289; Linguagem: Inglês

10.1016/j.lfs.2021.120213

1879-0631

Robson Barth, Carolina Ruoso, Sandra Mara Ferreira, Francieli Caroline de Ramos, Fernanda Barbosa Lima, Antônio C. Boschero, Gustavo Jorge dos Santos,

Diabetes Management and Research

Regardless of the etiology, any type of DM presents a reduction of insulin-secreting cell mass, so it is important to investigate pathways that induce the increase of this cell mass.Based on the fact that (1) HNF4α is crucial for β-cell proliferation, (2) DEX-induced IR promotes β-cell mass expansion, and (3) the stimulation of β-cell mass expansion may be an important target for DM therapies, we aimed to investigate whether DEX-induced proliferation of β pancreatic cells is dependent on HNF4α.We used WildType (WT) and Knockout (KO) mice for HNF4-α, treated or not with 100 mg/Kg/day of DEX, for 5 consecutive days. One day after the last injection of DEX the IR was confirmed by ipITT and the mice were euthanized for pancreas removal.In comparison to WT, KO mice presented increased glucose tolerance, lower fasting glucose and increased glucose-stimulates insulin secretion (GSIS). DEX induced IR in both KO and WT mice. In addition, DEX-induced β-cell mass expansion and an increase in the Ki67 immunostaining were observed only in WT mice, evidencing that IR-induced β-cell mass expansion is dependent on HNF4α. Also, we observed that DEX-treatment, in an HNF4α-dependent way, promoted an increase in PDX1, PAX4 and NGN3 gene expression.Our results strongly suggest that DEX-induced IR promotes β-cell mass expansion through processes of proliferation and neogenesis that depend on the HNF4α activity, pointing to HNF4α as a possible therapeutic target in DM treatment.