Pancreastatin inhibits insulin secretion from isolated rat islets: studies on its mechanism of action.
The peptide pancreastatin is known to inhibit insulin secretion. To study its mechanism of action, we examined the effects of pancreastatin on 45Ca(2+)- and 86Rb(+)-efflux from isolated rat islets. We found that glucose (8.3 mmol/l)-stimulated insulin secretion was totally abolished by pancreastatin (100 nmol/l). It is known that glucose reduces the 86Rb(+)-efflux and increases the 45Ca(2+)-efflux from prelabelled islets, which reflects its action on the K(+)- and Ca(2+)-permeabilities. We found that pancreastatin reduced the glucose-stimulated increase in 45Ca(2+)-efflux without affecting the 86Rb(+)-efflux. This shows that pancreastatin inhibits the action of glucose on Ca(2+)-channels, without influencing the closure of K(+)-channels induced by the sugar. The results indicate that pancreastatin does not inhibit insulin secretion by hyperpolarizing the B-cells, but rather that the peptide inhibits insulin secretion by inhibiting the glucose-stimulated B-cell Ca(2+)-uptake that evolves by depolarization.
Lindskog
S
S
Department of Medicine, Lund University, Malmö, Sweden.
Skoglund
G
G
Ahrén
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002250:Carbon Radioisotopes; D053379:Chromogranin A; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010187:Pancreatic Hormones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism; D012414:Rubidium Radioisotopes; D013997:Time Factors
D002250:Carbon Radioisotopes; D053379:Chromogranin A; D007328:Insulin; D010187:Pancreatic Hormones; D012414:Rubidium Radioisotopes; C050836:pancreastatin; D005947:Glucose; D012413:Rubidium; D003981:Diazoxide; D002118:Calcium