Nerve Growth Factor Promotes Development of Glucose Induced Insulin Secretion in Rat Neonate Pancreatic Beta Cells by Modulating Calcium Channels

Abstract

Neonatal javascript:app('lower case beta')ß cells are functionally immature as they secrete less insulin than adults and lack of glucose response. The mechanisms that participate in the functional maturation of these cells are not known. Adult rat javascript:app('lower case beta')ß cells synthesize and secrete nerve growth factor (NGF) and express NGF receptors. NGF increases glucose-induced insulin secretion by modulating electrical activity in adult javascript:app('lower case beta')ß cells. In this work, we explored if NGF is involved in the maturation of glucose-induced insulin secretion coupling in rat neonate javascript:app('lower case beta')ß-cells.Pancreatic javascript:app('lower case beta')ß-cells were cultured for 48 h in control conditions, either with NGF or a neutralizing NGF antibody. We measured glucose-stimulated insulin secretion and whole-cell Ca2+ currents. We also analyzed both synthesis and molecular expression of Ca2+ channel subunits.Compared to controls, NGF-treated neonate javascript:app('lower case beta')ß-cells increased insulin biosynthesis and secretion in response to glucose and increased Ca2+ current density by translocation of LD-type Ca2+ channels to the plasma membrane. This type of secretion is similar to that observed in adults.NGF contributes to in vitro maturation by inducing beta cells to secrete insulin accordant with external glucose concentration, in other words promoting glucose sensitivity. Similar NGF-autocrine mechanisms could be active in vivo, because these effects were blocked by a neutralizing NGF-antibody. Understanding mechanisms that contribute to normal development of javascript:app('lower case beta')ß cell could provide insights to recognize alterations concomitant with type-2 diabetes.