| Title | Glucocorticoids in Vivo Induce Both Insulin Hypersecretion and Enhanced Glucose Sensitivity of Stimulus-Secretion Coupling in Isolated Rat Islets. | | Author(s) | Rafacho A, Marroquí L, Taboga SR, Abrantes JL, Silveira LR, Boschero AC, Carneiro EM, Bosqueiro JR, Nadal A, Quesada I | | Institution | Instituto de Bioingeniería (A.R., L.M., A.N., I.Q.) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) (A.R., L.M., A.N., I.Q.), Universidad Miguel Hernández de Elche, Elche 03202, Spain; Departamento de Educação Física (A.R., J.R.B.), Faculdade de Ciências, Universidade Estadual Paulista, Bauru 17033-360, São Paulo, Brazil; Departamento de Biologia, Instituto de Biociências, Humanidades, e Ciências Exatas (S.R.T.), Universidade Estadual Paulista, São José do Rio Preto 15005-4000, São Paulo, Brazil; Departamento de Anatomia, Biologia Celular, e Fisiologia (J.L.F.A., A.C.B., E.M.C.), Instituto de Biologia, Universidade Estadual de Campinas, Campinas 13083-970, São Paulo, Brazil; and Faculdade de Educação Física e Esportes (L.R.S.), Universidade de São Paulo, Ribeirão Preto, 14040-900, São Paulo, Brazil. | | Source | Endocrinology 2009 Oct 30. | | Abstract | Although glucocorticoids are widely used as antiinflammatory agents in clinical therapies, they may cause serious side effects that include insulin resistance and hyperinsulinemia. To study the potential functional adaptations of the islet of Langerhans to in vivo glucocorticoid treatment, adult Wistar rats received dexamethasone (DEX) for 5 consecutive days, whereas controls (CTL) received only saline. The analysis of insulin release in freshly isolated islets showed an enhanced secretion in response to glucose in DEX-treated rats. The study of Ca(2+) signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca(2+) signals were found between both groups with tolbutamide or KCl, indicating that the alterations were probably related to metabolism. Thus, mitochondrial function was explored by monitoring oxidation of nicotinamide dinucleotide phosphate autofluorescence and mitochondrial membrane potential. Both parameters revealed a higher response to glucose in islets from DEX-treated rats. The mRNA and protein content of glucose transporter-2, glucokinase, and pyruvate kinase was similar in both groups, indicating that changes in these proteins were probably not involved in the increased mitochondrial function. Additionally, we explored the status of Ca(2+)-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase Calpha as well as an increased response of the phospholipase C/inositol 1,4,5-triphosphate pathway in DEX-treated rats. Finally, an increased number of docked secretory granules were observed in the beta-cells of DEX animals using transmission electron microscopy. Thus, these results demonstrate that islets from glucocorticoid-treated rats develop several adaptations that lead to an enhanced stimulus-secretion coupling and secretory capacity. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19880808 |
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