miR-124a expression contributes to the monophasic pattern of insulin secretion in islets from pregnant rats submitted to a low-protein diet
2018
de Siqueira, Kariny Cassia | de Lima, Faena Moura | Lima, Fernanda Souza | Taki, Marina Satie | da Cunha, Clarissa Felfili | de Lima Reis, Sílvia Regina | Camargo, Rafael Ludemann | Batista, Thiago Martins | Vanzela, Emerielle Cristine | Nardelli, Tarlliza Romanna | Carneiro, Everardo Magalhães | Bordin, Silvana | Ignácio-Souza, Letícia Martins | Latorraca, Márcia Queiroz
PURPOSE: To evaluate the role of miR-124a in the regulation of genes involved in insulin exocytosis and its effects on the kinetics of insulin secretion in pancreatic islets from pregnant rats submitted to a low-protein diet. METHODS: Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. Kinetics of the glucose-induced insulin release and measurement of [Ca²⁺]ᵢ in pancreatic islets were assessed by standard protocols. The miR-124a expression and gene transcriptions from pancreatic islets were determined by real-time polymerase chain reaction. RESULTS: In islets from LPP rats, the first phase of insulin release was abrogated. The AUC [Ca²⁺]ᵢ from the LPP group was lower compared with the other groups. miR-124a expression was reduced by a low-protein diet. SNAP-25 mRNA, protein expression, and Rab3A protein content were lower in the LPP rats than in CP rats. Syntaxin 1A and Kir6.2 mRNA levels were decreased in islets from low-protein rats compared with control rats, whereas their protein content was reduced in islets from pregnant rats. CONCLUSIONS: Loss of biphasic insulin secretion in islets from LPP rats appears to have resulted from reduced [Ca²⁺]ᵢ due, at least in part, to Kir6.2 underexpression and from the changes in exocytotic elements that are influenced either directly or indirectly by miR-124a.
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