Calcium Channels in Postnatal Development of Rat Pancreatic Beta Cells and Their Role in Insulin Secretion.

Neivys García-Delgado,Carlos Manlio Díaz-García,Carmen Sánchez-Soto,Myrian Velasco,Marcia Hiriart

doi:10.3389/fendo.2018.00040

Abstract

Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells. We observed that the percentage of detection of T-type current increased with the stage of development. T-type calcium current density in adult cells was higher than in neonatal and P20 beta cells. Mean HVA current density also increased with age. Calcium current behavior in P20 beta cells was heterogeneous; almost half of the cells had HVA current densities higher than the adult cells, and this was independent of the presence of T-type current. We detected the presence of α1G, α1H, and α1I subunits of LVA channels at all ages. The Cav 3.1 subunit (α1G) was the most expressed. T-type channel blockers mibefradil and TTA-A2 significantly inhibited insulin secretion at 5.6 mM glucose, which suggests a physiological role for T-type channels at basal glucose conditions. Both, nifedipine and TTA-A2, drastically decreased the beta-cell subpopulation that secretes more insulin, in both basal and stimulating glucose conditions. We conclude that changes in expression and activity of VGCC during the development play an important role in physiological maturation of beta cells.

Highlights

Pancreatic beta cells acquire functional maturity during the first month of life, allowing them to present a robust insulin secretion in response to increases in the extracellular glucose concentration
As T-type channels have not been studied in detail in early stages of development, we were interested in knowing the percentage of beta cells where this current is detectable
The percentage of detection of T-type current increased with the maturation of beta cell

Summary

Introduction

Pancreatic beta cells acquire functional maturity during the first month of life, allowing them to present a robust insulin secretion in response to increases in the extracellular glucose concentration. Beta cells of adult animals are mature and detect changes in the extracellular glucose level; presenting a biphasic secretion, consisting of a first fast phase and a second one sustained [1]. Animals become independent, and this is a driving force for beta cells to mature Another crucial development stage is the weaning period (20 days in rats, P20), where we have observed a physiological insulin resistance [3]. This is a critical postnatal window due to changes in animal food, a shift from a high-fat diet to high-carbohydrate diet, which may lead to changes in the cellular response machinery, including receptors, enzymes, and ion channels activity

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