Glucose-induced oscillatory insulin secretion in perifused rat pancreatic islets and clonal beta-cells (HIT).
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.
Evans Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.
B A
BA
Cunningham
J T
JT
Deeney
C R
CR
Bliss
B E
BE
Corkey
K
K
Tornheim
D000818:Animals; D002118:Calcium / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D002999:Clone Cells; D005947:Glucose / Q000008:administration & dosage / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D008297:Male; D010477:Perfusion; D010507:Periodicity; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D005947:Glucose; D002118:Calcium