Glucose-dependent promotion of insulin release from mouse pancreatic islets by the insulin-mimetic compound L-783,281.
An insulin-mimetic compound (L-783,281) was used in an attempt to determine the role of the beta-cell insulin receptor (IR) on insulin release. Islets were isolated from C57Bl/6j mice and cultured for 1 to 4 days. Insulin release from individual islets perifused in the presence of 3 mmol/l glucose was 10.5 plus minus 1.4 pg/min. Addition of 10 micromol/l L-783,281 had no effect on the rate of insulin secretion. When L-783,281 was added to perifusion medium containing 11 mmol/l glucose, the insulin-mimetic compound significantly increased insulin release. Insulin release from the isolated islet is pulsatile. In the presence of 3 mmol/l glucose, addition of L-783,281 significantly decreased the frequency of the oscillations from 0.35 plus minus 0.03 to 0.22 plus minus 0.04 oscillations/min. Addition of L-783,281 to perifusion medium containing 11 mmol/l glucose had no effect on the frequency of the insulin pulses (0.30 plus minus 0.05 oscillations/min). These results indicate that activation of the beta-cell IR by L-783,281 augments insulin release in the presence of a stimulatory glucose concentration. At nonstimulatory glucose concentrations, activation of the beta-cell IR may affect mechanisms related to the frequency of the insulin pulses.
Westerlund
Johanna
J
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. johanna.westerlund@medcellbiol.uu.se
Wolf
Bryan A
BA
Bergsten
Peter
P
D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D011673:Pulsatile Flow
D007211:Indoles; D007328:Insulin; C119066:L 783281; D005947:Glucose