Effect of PAO (phenylarsine oxide) on the inhibitory effect of insulin and IGF-1 on insulin release from INS-1 cells.
Phenylarsine oxide (PAO) which complexes vicinal thiol groups is a valuable pharmacological tool to investigate the interaction of peptides such as insulin with their receptors and the signal transduction from the receptor to the cell interior. This tool was now used to elucidate the inhibitory effects of insulin and IGF-1 on insulin secretion via their receptors. Insulin and IGF-1 inhibited insulin release from INS-1 cells, an insulin secreting cell line. PAO was able to reverse this inhibitory effect of both hormones. Dimercaptopropanol (DMP), which is well known to antagonize PAO effects, inhibited the abolishment of PAO effect on the inhibitory effect of insulin and IGF-1 regarding insulin release. Membrane bound GLUT2 in INS-1 cells was increased by either insulin and IGF-1 which is counteracted by PAO. Thus the inhibitory effect of insulin and IGF-1 on insulin release is operative and can be disturbed by a thiol interacting compound such as PAO. This may happen at the receptor level or at the sub-receptor level.
Department of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Germany.
Eugen J
EJ
Verspohl
D000818:Animals; D001152:Arsenicals / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D004112:Dimercaprol / Q000494:pharmacology; D004347:Drug Interactions; D025461:Feedback, Physiological / Q000502:physiology; D051246:Glucose Transport Proteins, Facilitative / Q000187:drug effects / Q000502:physiology; D051273:Glucose Transporter Type 2 / Q000032:analysis; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology* / Q000502:physiology; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011863:Radioimmunoassay; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000502:physiology; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D001152:Arsenicals; D051246:Glucose Transport Proteins, Facilitative; D051273:Glucose Transporter Type 2; D007328:Insulin; D004112:Dimercaprol; C029341:oxophenylarsine; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin