AJP - Endocrinology and Metabolism, Vol 271, Issue 4 E702-E710, Copyright © 1996 by American Physiological Society
Glucose-induced oscillatory insulin secretion in perifused rat pancreatic islets and clonal beta-cells (HIT)
B. A. Cunningham, J. T. Deeney, C. R. Bliss, B. E. Corkey and K. Tornheim
Evans Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.
Normal insulin secretion is oscillatory in vivo and from groups of
perifused islets. Stimulation of rat islets with different glucose
concentrations gave insulin oscillations of similar period (5-8 min) but
increasing amplitude. It has been assumed that oscillatory secretion is due
to oscillations in intracellular free Ca2+, as seen in single islets and
single pancreatic beta-cells. However, when islets were perifused with
diazoxide and high KCl to maintain high intracellular free Ca2+, insulin
oscillations of similar amplitude and period still occurred on glucose
stimulation, although superimposed on elevated basal secretion. Several
likely possibilities for a diffusible synchronizing factor were tested,
including pyruvate, lactate, ATP, and insulin itself; nevertheless,
perifusion with high concentrations of these did not prevent insulin
oscillations. Clonal pancreatic beta-cells (HIT) and dissociated islets
also exhibited oscillatory insulin secretion, but with the 5- to 8-min
period oscillations superimposed on 15- to 20-min period oscillations.
These results indicate that the mechanisms for generating and synchronizing
insulin oscillations reside in the beta-cell, although the structure of the
islet may modulate the oscillation pattern.
