Inhibitory effect of amylin (islet amyloid polypeptide) on insulin response to non-glucose stimuli. Study in perfused rat pancreas.
Amylin, also called islet amyloid polypeptide (IAPP), can inhibit the glucose-induced insulin secretion in perfused rat pancreas at 75 pmol/l, a concentration comparable to that found in the effluent of this experimental model. To further explore the influence of amylin on insulin release, we investigated the effect of synthetic rat amylin (75 pmol/l) on insulin response to non-glucose secretagogues. These agents stimulate B-cell secretion via different mechanisms, such as a dihydropyridine derivative (BAY K 8644, 10 mmol/l) which activates Ca(2+)-channels, a sulfonylurea (tolbutamide, 0.2 mmol/l) which blocks ATP-dependent K(+)-channels, KCL (11 mmol/l) which depolarizes B cells and the 26-33 fragment of cholecystokinin (8-CCK, 1 nmol/l) which increases phospholipid turnover. The study was performed in perfused rat pancreas. Amylin significantly inhibited insulin response to BAY K 8644 (65%), KCI (60%) and 8-CCK (80%) as well as the early phase of tolbutamide-induced insulin output (70%). Thus, amylin can inhibit insulin release induced by secretagogues that interact at different levels of B-cell stimulus-secretion coupling. This inhibition may be due to a multifarious influence of amylin on the B-cell secretory mechanism and/or a disturbing effect on a distal, crucial step in the insulin-releasing mechanism, e.g. by affecting exocytosis of the secretory granule or by inhibiting an essential metabolic pathway within the B cell.
Hospital Puerta de Hierro, Universidad Autónoma de Madrid, Spain.
M
M
Salas
R A
RA
Silvestre
O
O
Garcia-Hermida
T
T
Fontela
J
J
Rodriguez-Gallardo
J
J
Marco
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008297:Male; D010477:Perfusion; D010743:Phospholipids / Q000378:metabolism; D026902:Potassium Channel Blockers; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology*; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology*
D000682:Amyloid; D002120:Calcium Channel Agonists; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D010743:Phospholipids; D026902:Potassium Channel Blockers; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014044:Tolbutamide; D005947:Glucose; D012844:Sincalide