Evaluation of different dexametasone concentration effects on pancreatic islets physiologycal parameters

• Grant number: 05/01199-9
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2006
• End date: December 31, 2007
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: José Roberto Bosqueiro
• Grantee: José Roberto Bosqueiro
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

Glucocorticoids are widely used in clinical practice due to its powerful immunosupressor and anti-inflammatory effects. However, depending on the dose and/or time of administration, diverse collateral risk effects are observed. Although to be a hormone class well studied, their effects on the physiology of endocrine pancreas are still unknown. Several works performed in vitro demonstrated direct effect of dexamethasone on insulin secretion. However, the description of these effects in experimental models in vivo is scarce. Dexamethasone can indirectly act on insulin secretion based in its diabetogenic action, thus consisting in an interesting model for the study of Diabetes. On the other hand, its direct action modulating gene expression can intervene with the results obtained in this model. Studies carried in our laboratory using dexamethasone in a dose of 1 mg/kg of body weigh, ip, for 5 days, indicate deleterious action on pancreatic islets when the glucocorticoid is administered in high concentrations. With the aim of diminish such deleterious effects on the islets, in this study we intend to evaluate the effect of different concentrations of dexamethasone on physiological parameters of pancreatic islets such as insulin secretion, mRNAs and proteins expression. Histological, histochemical, stereological and morphometric procedures will be applied. Also, diverse metabolic parameters will be investigated such GTT, hepatic glycogen and fat, among others. Such study could be of great value since we can find a dose of dexamethasone that produces periferical resistance to insulin action, hyperglycemia and, consequently hyperinsulinemia without, however, producing the joined deleterious effect in pancreatic islets observed in our current model. (AU)