Autocrine regulation of single pancreatic beta-cell survival.
Function and survival of cells depend in part on the presence of growth factors. We explored the autocrine regulation of insulin and nerve growth factor (NGF) on single adult rat pancreatic beta-cell survival and hormone secretion. When NGF or insulin signaling were blocked in culture media, cell survival decreased compared with control cells, with apoptosis being the main mechanism of cell death. To further explore the role of glucose in beta-cell survival, we cultured the cells for 16 h in 2.6 mmol/l glucose and observed that nearly 17% of the cells developed apoptosis; this effect was partially prevented by NGF and almost completely inhibited by insulin treatment. A high K+ concentration had the same effect, suggesting that insulin and NGF secretion by the cells was responsible for the survival effects and not glucose per se. Blocking NGF signaling with an NGF antibody or with K252a reduced insulin biosynthesis and secretion in the cells that survived the treatment. Moreover, the functional beta-cell subpopulation with a higher insulin secretion rate is more susceptible to K252a. These results further indicate that NGF and insulin play important autoregulatory roles in pancreatic beta-cell survival and function and strongly suggest the need to explore new focuses in diabetes treatment.
Navarro-Tableros
Víctor
V
Biophysics Department, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, DF, Mexico.
Sánchez-Soto
M Carmen
MC
García
Santiago
S
Hiriart
Marcia
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006462:Hemolytic Plaque Technique; D006706:Homeostasis; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D007328:Insulin; D020932:Nerve Growth Factor