NGF effects promote the maturation of rat pancreatic beta cells by regulating GLUT2 levels and distribution, and glucokinase activity

• Published in: PloS one Vol. 19; no. 6; p. e0303934
• Main Authors: Samario-Román, Jazmín, Velasco, Myrian, Larqué, Carlos, Cárdenas-Vázquez, René, Ortiz-Huidobro, Rosa Isela, Hiriart, Marcia
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 14.06.2024; Public Library of Science (PLoS)
• Subjects: Age composition; Animals; Beta cells; Biology and Life Sciences; Calcium; Calcium currents; Cell survival; Cells; Channel gating; Dextrose; Ethylenediaminetetraacetic acid; Experiments; Glucokinase; Glucose; Glucose metabolism; Glucose transporter; Glycolysis; Growth factors; Immunofluorescence; Insulin; Insulin resistance; Insulin secretion; International organizations; Islet cells; Isoenzymes; Maturation; Medicine and Health Sciences; Metabolism; Neonates; Nerve growth factor; Pancreas; Pancreatic beta cells; Physical Sciences; Physiological aspects; Physiology; Research and Analysis Methods; Rodents; Suckling behavior; Weaning
• DOI: 10.1371/journal.pone.0303934
• ISSN: 1932-6203

The nerve growth factor (NGF) participates in cell survival and glucose-stimulated insulin secretion (GSIS) processes in rat adult beta cells. GSIS is a complex process in which metabolic events and ionic channel activity are finely coupled. GLUT2 and glucokinase (GK) play central roles in GSIS by regulating the rate of the glycolytic pathway. The biphasic release of insulin upon glucose stimulation characterizes mature adult beta cells. On the other hand, beta cells obtained from neonatal, suckling, and weaning rats are considered immature because they secrete low levels of insulin and do not increase insulin secretion in response to high glucose. The weaning of rats (at postnatal day 20 in laboratory conditions) involves a dietary transition from maternal milk to standard chow. It is characterized by increased basal plasma glucose levels and insulin levels, which we consider physiological insulin resistance. On the other hand, we have observed that incubating rat beta cells with NGF increases GSIS by increasing calcium currents in neonatal cells. In this work, we studied the effects of NGF on the regulation of cellular distribution and activity of GLUT2 and GK to explore its potential role in the maturation of GSIS in beta cells from P20 rats. Pancreatic islet cells from both adult and P20 rats were isolated and incubated with 5.6 mM or 15.6 mM glucose with and without NGF for 4 hours. Specific immunofluorescence assays were conducted following the incubation period to detect insulin and GLUT2. Additionally, we measured glucose uptake, glucokinase activity, and insulin secretion assays at 5.6 mM or 15.6 mM glucose concentrations.