Cited by 80Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes and associated disorders

Glucocorticoids in Vivo Induce Both Insulin Hypersecretion and Enhanced Glucose Sensitivity of Stimulus-Secretion Coupling in Isolated Rat Islets

Rafacho, Alex, Marroquí, Laura, Taboga, Sebastião R., Abrantes, Júlia L. F., Silveira, Leonardo R., Boschero, Antonio C., Carneiro, Everardo M., Bosqueiro, José R. +2 more·2010·Endocrinology

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 Ca2+ signals by fluorescence microscopy also demonstrated a higher response to glucose in islets from DEX-treated animals. However, no differences in Ca2+ 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 Ca2+-dependent signaling kinases. Unlike calmodulin kinase II, we found an augmented phosphorylation level of protein kinase Cα 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 β-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.

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Crossref · 10.1210/en.2009-0704

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Authors
Rafacho, A., Marroquí, L., Taboga, S. R., Abrantes, J. L. F., Silveira, L. R., Boschero, A. C., Carneiro, E. M., Bosqueiro, J. R., Nadal, A., & Quesada, I.
Affiliations
  • Universitat de Miguel Hernández d'Elx (ES)
  • Instituto de Bioingeniería (A.R., L.M., A.N., I.Q.), Universidad Miguel Hernández de Elche, Elche 03202, Spain
  • 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
  • Universidade de São Paulo (BR)
  • Universidade Estadual de Campinas (UNICAMP) (BR)
  • Departamento de Educação Física (A.R., J.R.B.), Faculdade de Ciências, Universidade Estadual Paulista, Bauru 17033-360, São Paulo, Brazil
Corresponding author
Rafacho, Alex
Venue
Endocrinology
Published
2010-01-01
Volume
151
Issue
1
Pages
85-95
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2077012846
Cited by
80
References
53
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 6 · 2014: 12 · 2013: 7 · 2012: 6
FWCI
4.72
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
  • Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) (submittedVersion)
  • UNESP Institutional Repository (São Paulo State University) (submittedVersion)
Funders
  • Ministerio de Ciencia e Innovación
  • Universidade Estadual Paulista
  • Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
  • Instituto de Salud Carlos III
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
glucocorticoids, dexamethasone, insulin secretion, stimulus-secretion coupling, pancreatic islets, pancreatic beta cells, glucose-stimulated insulin secretion, calcium signaling, mitochondrial function, protein kinase C alpha, secretory granules, hyperinsulinemia, insulin resistance
MeSH terms
Insulin Secretion, Adaptation, Biological, Animals, Calcium, Cell Separation, Cells, Cultured, Dexamethasone, Drug Resistance, Drug Synergism, Glucocorticoids, Glucose, Insulin, Insulin Resistance, Islets of Langerhans, Male, Mitochondria, Signal Transduction, Up-Regulation, Rats, Wistar, Rats

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