Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat beta-cells.
Insulin secretion in mature beta-cells increases vigorously when extracellular glucose concentration rises. Glucose-stimulated insulin secretion depends on Ca(2+) influx through voltage-gated Ca(2+) channels. During fetal development, this structured response is not well established, and it is after birth that beta-cells acquire glucose sensitivity and a robust secretion. We compared some elements of glucose-induced insulin secretion coupling in beta-cells obtained from neonatal and adult rats and found that neonatal cells are functionally immature compared with adult cells. We observed that neonatal cells secrete less insulin and cannot sense changes in extracellular glucose concentrations. This could be partially explained because in neonates Ca(2+) current density and synthesis of mRNA alpha1 subunit Ca(2+) channel are lower than in adult cells. Interestingly, immunostaining for alpha1B, alpha1C, and alpha1D subunits in neonatal cells is similar in cytoplasm and plasma membrane, whereas it occurs predominantly in the plasma membrane in adult cells. We also observed that GLUT2 expression in adult beta-cells is mostly located in the membrane, whereas in neonatal cells glucose transporters are predominantly in the cytoplasm. This could explain, in part, the insensitivity to extracellular glucose in neonatal beta-cells. Understanding neonatal beta-cell physiology and maturation contributes toward a better comprehension of type 2 diabetes physiopathology, where alterations in beta-cells include diminished L-type Ca(2+) channels and GLUT2 expression that results in an insufficient insulin secretion.
Navarro-Tableros
Victor
V
Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Fiordelisio
Tatiana
T
Hernández-Cruz
Arturo
A
Hiriart
Marcia
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004553:Electric Conductivity; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D007158:Immunologic Techniques; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling
D015220:Calcium Channels; D051273:Glucose Transporter Type 2; D007328:Insulin; D020033:Protein Isoforms; D012333:RNA, Messenger; C495683:Slc2a2 protein, rat