title: Morphofunctional alterations in endocrine pancreas of short- and long-term dexamethasone-treated rats.
abstract: Long-term dexamethasone therapy may induce peripheral insulin resistance (IR), which in turn elicits increased beta-cell function and proliferation. However, whether such adaptive compensations occur during short-term treatment with dexamethasone is unclear. Here, we compared morphofunctional parameters in endocrine pancreas after short- and long-term dexamethasone administration. Groups of rats received daily i. p. injection of 1 mg/kg b. w. dexamethasone for 1 (DEX-1), 3 (DEX-3), or 5 consecutive days (DEX-5), whilst control rats were saline-treated (CTL). Despite the absence of apparent IR in DEX-1 rats, this group exhibited increased circulating insulin levels and glucose-stimulated insulin secretion (GSIS), compared to the CTL group (p<0.05). Evident IR as well as marked hyperinsulinemia and GSIS, as judged by the static and dynamic insulin secretion values, were observed in DEX-3 and DEX-5 rats (p<0.05). GSIS in islets cultured with 1 μM dexamethasone was lower compared to the control (p<0.05). Marked increases in beta-cell proliferation were observed in DEX-3 and DEX-5 rats, compared to CTL and DEX-1 rats (p<0.05). The alterations observed in DEX-3 rats were more pronounced in DEX-5 rats, which also exhibited a higher content of islet Cdk4 and Cd2 proteins, compared to the CTL group (p<0.05). We conclude that short-term dexamethasone treatment (DEX-1) induces an increase in beta-cell function that does not require the presence of discernible IR. As the treatment continues, the IR develops rapidly, and increased insulin secretion as well as beta-cell hyperplasia is demanded for the appropriate maintenance of glucose homeostasis.
authors.affiliation: Department of Physical Education, School of Sciences, UNESP - Universidade Estadual Paulista, Bauru, SP, Brazil. rafacho@ccb.ufsc.br
authors.forename: A
authors.initials: A
authors.lastname: Rafacho
authors.forename: J L F
authors.initials: JL
authors.lastname: Abrantes
authors.forename: D L
authors.initials: DL
authors.lastname: Ribeiro
authors.forename: F M
authors.initials: FM
authors.lastname: Paula
authors.forename: M E
authors.initials: ME
authors.lastname: Pinto
authors.forename: A C
authors.initials: AC
authors.lastname: Boschero
authors.forename: J R
authors.initials: JR
authors.lastname: Bosqueiro
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013995:Time
chemical_list: D007328:Insulin; D003907:Dexamethasone; D005947:Glucose