Tricyclic antidepressant imipramine reduces the insulin secretory rate in islet cells of Wistar albino rats through a calcium antagonistic action.
OBJECTIVE
Treatments with antidepressants have been associated with modifications in glucose homeostasis. The aim of this study was to assess the effect of imipramine, a tricyclic antidepressant, on insulin-secreting cells.


METHODS
Insulin radioimmunoassay, radioisotopic, fluorimetric and patch-clamp methods were used to characterise the effects of imipramine on ionic and secretory events in pancreatic islet cells from Wistar albino rats.


RESULTS
Imipramine induced a dose-dependent decrease in glucose-stimulated insulin output (IC(50)=5.2 micromol/l). It also provoked a concentration-dependent reduction in (45)Ca outflow from islets perifused in the presence of 16.7 mmol/l glucose. Moreover, imipramine inhibited the increase in (45)Ca outflow mediated by K(+) depolarisation. Patch-clamp recordings further revealed that imipramine provoked a marked and reversible decrease of the inward Ca(2+) current. In single islet cells, imipramine counteracted the rise in [Ca(2+)](i) evoked by glucose or high K(+) concentrations.


CONCLUSIONS
These data indicate that imipramine dose-dependently reduces the insulin secretory rate from rat pancreatic beta cells. Such an effect appears to be mediated by the inhibition of voltage-sensitive Ca(2+) channels with subsequent reduction in Ca(2+) entry. Thus, it is possible that some adverse effects of imipramine are related, at least in part, to its capacity to behave as a Ca(2+) entry blocker.
Antoine
M-H
MH
Laboratory of Pharmacology, Faculty of Medicine, CP 617, Université Libre de Bruxelles, Lennik Street 808, 1070 Brussels, Belgium.
Gall
D
D
Schiffmann
S N
SN
Lebrun
P
P
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D007099:Imipramine / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D011188:Potassium / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D000929:Antidepressive Agents, Tricyclic; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007328:Insulin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D007099:Imipramine; D011188:Potassium; D002118:Calcium