Different signaling pathways involved in glucose- and cell swelling-induced insulin secretion by rat pancreatic islets in vitro.
BACKGROUND
The objective was to compare signal transduction pathways exploited by glucose and cell swelling in stimulating insulin secretion.


METHODS
Isolated rat (Wistar) pancreatic islets were stimulated in vitro by 20 mmol/l glucose or 30% hypotonic medium (202 mOsm/kg) in various experimental conditions.


RESULTS
Glucose did not stimulate insulin release in calcium free medium. Cell swelling-induced insulin release in calcium free medium, even in the presence of the membrane permeable calcium chelator BAPTA/AM (10 micromol/l). Protein kinase C (PKC) inhibitor bisindolylmaleimide VIII (1 micromol/l) abolished the stimulation of insulin secretion by glucose but did not affect the swelling-induced insulin release. PKC activator phorbol 12-13-dibutyrate (1 micromol/l) stimulated insulin secretion in medium containing Ca2+ and did not potentiate insulin secretion stimulated by hypotonic extracellular fluid. Dilution of the medium (10-30%) had an additive effect on the glucose-induced insulin secretion. Noradrenaline (1 micromol/l) abolished glucose-induced insulin secretion but did not inhibit hypotonic stimulation either in presence or absence of Ca2+.


CONCLUSIONS
Glucose- and swelling-induce insulin secretion through separate signal transduction pathways. Hyposmotic stimulation is independent from both the extracellular and intracellular Ca2+, does not involve PKC activation, and could not be inhibited by noradrenaline. These data indicate a novel signaling pathway for stimulation of insulin secretion exploited by cell swelling.
Bacová
Zuzana
Z
Institute of Experimental Endocrinology, Centre of Excellence acknowledged by European Commission, Slovak Academy of Sciences, Bratislava, Slovakia.
Benický
Július
J
Lukyanetz
Elena E
EE
Lukyanetz
Igor A
IA
Strbák
Vladimir
V
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D048429:Cell Size; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007038:Hypotonic Solutions; D007211:Indoles; D007328:Insulin; D008301:Maleimides; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D015240:Phorbol 12,13-Dibutyrate; D004533:Egtazic Acid; D011493:Protein Kinase C; D005947:Glucose; D002118:Calcium; D009638:Norepinephrine; C064755:Ro 31-7549