Reduced Insulin Secretion in Protein Malnourished Mice Is Associated with Multiple Changes in the beta-Cell Stimulus-Secretion Coupling

Author(s):Show less -

Soriano, Sergi ^{[1, 2]} ; Gonzalez, Alejandro ^{[1, 2]} ; Marroqui, Laura ^{[1, 2]} ; Tuduri, Eva ^{[1, 2]} ; Vieira, Elaine ^{[1, 2]} ; Amaral, Andressa G. ^{[3, 4]} ; Batista, Thiago M. ^{[3, 4]} ; Rafacho, Alex ^{[4, 5]} ; Boschero, Antonio C. ^{[3, 4]} ; Nadal, Angel ^{[1, 2]} ; Carneiro, Everardo M. ^{[3, 4]} ; Quesada, Ivan ^{[1, 2]}

Affiliation

^[1] Univ Miguel Hernandez, Inst Bioingn, Elche 03202 - Spain

^[2] Univ Miguel Hernandez, CIBER Diabet Enfermedades Metab Asociadas CIBERDE, Elche 03202 - Spain

^[3] Univ Estadual Campinas, Dept Anat Biol Celular Fisiol Biofis, Inst Biol, BR-13083970 Campinas, SP - Brazil

^[4] Inst Nacl Ciencia Tecnol Obesidade & Diabet, Sao Paulo - Brazil

^[5] Univ Estadual Paulista, Dept Educacao Fis, Fac Ciencias, BR-17033360 Sao Paulo - Brazil

• Document type: Journal article
• Source: Endocrinology; v. 151, n. 8, p. 3543-3554, AUG 2010.
• Web of Science Citations: 23

Abstract

The mechanism by which protein malnutrition impairs glucose-stimulated insulin secretion in the pancreatic beta-cell is not completely known but may be related to alterations in the signaling events involved in insulin release. Here, we aimed to study the stimulus-secretion coupling of beta-cells from mice fed with low-protein (LP) diet or normal-protein (NP) diet for 8 wk after weaning. Patch-clamp measurements in isolated cells showed that beta-cells from LP mice had a resting membrane potential that was more hyperpolarized than controls. Additionally, depolarization and generation of action potentials in response to stimulatory glucose concentrations were also impaired in beta-cells of LP mice. All these alterations in the LP group were most likely attributed to higher ATP-dependent K(+) (K(ATP)) channel activity in resting conditions and lower efficiency of glucose to induce the closure of these channels. Moreover, a Western blot analysis revealed higher protein levels of the sulphonylurea receptor of the K(ATP) channel in islets of LP mice. Because beta-cell Ca(2+) signals depend on electrical activity, intracellular Ca(2+) oscillations were measured by fluorescence microscopy in intact islets, indicating a lower response to glucose in the LP group. Finally, cell-to-cell synchrony of Ca(2+) signals was analyzed by confocal microscopy. Islets from LP mice exhibited a decreased level of coupling among beta-cells, which was probably due to the low expression levels of connexin 36. Therefore, low-protein diet leads to several alterations in the stimulus-secretion coupling of pancreatic beta-cells that might explain the diminished insulin secretion in response to glucose in this malnutrition state. (Endocrinology 151: 3543-3554, 2010) (AU)