Cosecretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets following stimulation or inhibition of beta-cell function.
The aim of this work was to simultaneously study the secretion of islet amyloid polypeptide (IAPP) and insulin from isolated rat pancreatic islets in vitro. For examination of stimulated beta-cells, nutrient secretagogues (16.7 mM glucose, 10 mM leucine + 2 mM glutamine), phosphodiesterase inhibition (5 mM theophylline), a sulphonylurea (0.5 microgram/ml glipizide), a non-nutrient amino acid (10 mM arginine), cholinergic stimulation (0.1 mM carbamylcholine) and insulinotropic peptides (0.1 microM vasoactive intestinal polypeptide and 0.1 microM glucagon), were used. For beta-cell suppression glucose phosphorylation inhibition (10 mM mannoheptulose), depletion of extracellular calcium, activation of the ATP-regulated K(+)-channel (0.5 mM diazoxide), adrenoreceptor stimulation (3 microM adrenaline), paracrine modulation (0.1 microM somatostatin), short-term treatment with a selective beta-cytotoxin (1.1 and 2.2 mM streptozotocin) and long-term treatment with a cytokine (25 U/ml interleukin-1 beta), were studied. The compounds with known effects on insulin secretion exerted their expected actions and this was paralleled by similar relative changes, with a possible exception for glucagon, in the IAPP secretion. The ratio of IAPP/insulin released did not change significantly under any of the tested experimental conditions, except for a slight increase following carbamylcholine stimulation. On a molar basis approx. 1% of IAPP was released when compared with insulin. These results are consistent with the hypothesis that the regulation of IAPP secretion from beta-cells of isolated rat pancreatic islets is essentially regulated by the same mechanisms as insulin secretion.
Stridsberg
M
M
Department of Clinical Chemistry, Uppsala University, Sweden.
Sandler
S
S
Wilander
E
E
D000596:Amino Acids / Q000494:pharmacology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000494:pharmacology
D000596:Amino Acids; D000682:Amyloid; D007328:Insulin; D007375:Interleukin-1; D058228:Islet Amyloid Polypeptide; D009479:Neuropeptides; D013311:Streptozocin; D008356:Mannoheptulose; D002217:Carbachol; D005947:Glucose; D003981:Diazoxide; D002118:Calcium