Role of the glutamte and glycine ionotropic receptors in the glucose-stimulated insulin secretion in INS-1E cells

Abstract

Pancreatic islets contain four different endocrine cell types. Their secretion is triggered by the firing of action potentials. Amongst them are the ² cells that secrete insulin, the only hypoglycemiant hormone in the organism. Low insulin secretion is one of the hallmarks of Diabetes Mellitus. The islet cells can regulate their own function through substances that act in a paracrine way. The main stimulus for insulin secretion is glucose in high plasma concentrations. However, several transmitters contribute to the modulation of this secretion, such as glutamate and glycine. Glutamate is the main excitatory neurotransmitter in the central nervous system and it has been suggested that this aminoacid could act as a signaling molecule also in the islets. Glutamate can act through its ionotropic receptors, whose expression has been described in pancreatic ² cells. Furthermore, inconclusive effects of glutamate on insulin secretion have been reported. An analysis of those results lead us to propose that those receptors could have different functions in high and low glucose concentrations, and there could be some cellular mechanism that would activate them in high glucose concentrations. Moreover, excitatory effects of glycine have also been reported on the insulin secretion, although it is considered to be an inhibitory aminoacid in the central nervous system. All the necessary machinery for glycine secretion is present on alfa and beta cells, which indicates that this aminoacid could have autocrine and paracrine functions on ² cells. Little is known about the expression of ionotropic glycine receptors in those cells, which until now has only been reported in one cell-line. In the present project the expression of ionotropic receptors of both neurotransmitters and their effects on insulin secretion in high and low glucose concentrations will be evaluated in the INS-1E ²-cell line.