Document Detail


High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets.
MedLine Citation:
PMID:  19158320     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of insulin signaling and cell cycle intermediates is required for adult beta-cell proliferation. Here, we report a model to study beta-cell proliferation in living rats by administering three different doses of dexamethasone (0.1, 0.5, and 1.0 mg/kg ip, DEX 0.1, DEX 0.5, and DEX 1.0, respectively) for 5 days. Insulin sensitivity, insulin secretion, and histomorphometric data were investigated. Western blotting was used to analyze the levels of proteins related to the control of beta-cell growth. DEX 1.0 rats, which present moderate hyperglycemia and marked hyperinsulinemia, exhibited a 5.1-fold increase in beta-cell proliferation and an increase (17%) in beta-cell size, with significant increase in beta-cell mass, compared with control rats. The hyperinsulinemic but euglycemic DEX 0.5 rats also showed a significant 3.6-fold increase in beta-cell proliferation. However, DEX 0.1 rats, which exhibited the lowest degree of insulin resistance, compensate for insulin demand by improving only islet function. Activation of the insulin receptor substrate 2/phosphatidylinositol 3-kinase/serine-threonine kinase/ribosomal protein S6 kinase pathway, as well as protein retinoblastoma in islets from DEX 1.0 and DEX 0.5, but not in DEX 0.1, rats was also observed. Therefore, increasing doses of dexamethasone induce three different degrees of insulin requirement in living rats, serving as a model to investigate compensatory beta-cell alterations. Augmented beta-cell mass involves beta-cell hyperplasia and, to a lower extent, beta-cell hypertrophy. We suggest that alterations in circulating insulin and, to a lesser extent, glucose levels could be the major stimuli for beta-cell proliferation in the dexamethasone-induced insulin resistance.
Authors:
Alex Rafacho; Tânia M Cestari; Sebastião R Taboga; Antonio C Boschero; José R Bosqueiro
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-21
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  296     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-25     Completed Date:  2009-05-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E681-9     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, Institute of Biology, University of Campinas, Rua Monteiro Lobato, s/n. Cidade Universitária, Campinas, São Paulo, Brazil, 13083-970. rafacho@unicamp.br
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / drug effects
Cell Death / drug effects
Cell Proliferation / drug effects*
Dexamethasone / administration & dosage,  pharmacology*
Dose-Response Relationship, Drug
Insulin Resistance
Insulin-Secreting Cells / drug effects*,  pathology,  physiology
Islets of Langerhans / anatomy & histology,  drug effects*,  pathology,  physiology
Male
Metabolic Syndrome X / chemically induced,  pathology
Organ Size
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
50-02-2/Dexamethasone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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