Horm Metab Res 2011; 43(4): 275-281
DOI: 10.1055/s-0030-1269896
Animals

© Georg Thieme Verlag KG Stuttgart · New York

Morphofunctional Alterations in Endocrine Pancreas of Short- and Long-term Dexamethasone-treated Rats

A. Rafacho1 , 2 , 3 , J. L. F. Abrantes2 , D. L. Ribeiro4 , 5 , F. M. Paula2 , M. E. Pinto4 , A. C. Boschero2 , J. R. Bosqueiro1
  • 1Department of Physical Education, School of Sciences, UNESP – Universidade Estadual Paulista, Bauru, SP, Brazil
  • 2Department of Anatomy, Cellular Biology and Physiology and Biophysics, Institute of Biology, UNICAMP – Universidade Estadual de Campinas, Campinas, SP, Brazil
  • 3Present Address: Department of Physiological Sciences, Center of Biological Sciences, UFSC – Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
  • 4Department of Biology, Institute of Biosciences, Letters and Exact Sciences, UNESP, São José do Rio Preto, SP, Brazil
  • 5Present Address: Department of Histology, Institute of Biomedical Sciences, UFU – Universidade Federal de Uberlândia, Uberlândia, MG, Brazil
Further Information

Publication History

received 13.08.2010

accepted 22.11.2010

Publication Date:
10 January 2011 (online)

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.

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Correspondence

A. Rafacho

Departamento de Ciências

Fisiológicas

Centro de Ciências Biológicas

–CCB

Universidade Federal de Santa

Catarina (UFSC)

88040-900 Florianópolis SC

Brazil

Phone: +55/48/3721 9444

Fax: +55/48/3721 9672

Email: rafacho@ccb.ufsc.br

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