Effects of tolbutamide and N-benzoyl-D-phenylalanine (NBDP) on the regulation of [Ca2+](i) oscillations in mouse pancreatic islets

Citation
S. Lenzen et T. Peckmann, Effects of tolbutamide and N-benzoyl-D-phenylalanine (NBDP) on the regulation of [Ca2+](i) oscillations in mouse pancreatic islets, BIOCH PHARM, 62(7), 2001, pp. 923-928
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
7
Year of publication
2001
Pages
923 - 928
Database
ISI
SICI code
0006-2952(20011001)62:7<923:EOTAN(>2.0.ZU;2-I
Abstract
The sulfonylurea. derivative, tolbutamide, and the phenylalanine derivative , N-benzoyl-D-phenylalanine (NBDP), both of which stimulate insulin secreti on through interaction with the sulfonylurea receptor (SUR1), were studied for their ability to increase the [Ca2+](i) and to interact with the glucos e-induced slow large amplitude [Ca2+](i) oscillations in isolated mouse pan creatic islets. Tolbutamide as wen as NBDP induced [Ca2+](i) oscillations o f extremely slow frequency. Both compounds also lowered the threshold for t he glucose-induced slow large amplitude [Ca2+], oscillations and significan tly reduced their frequency in intact islets as well as in single pancreati c beta cells. These [Ca2+](i) oscillations apparently require a glucokinase -mediated glycolytic flux. This conclusion is supported by the observations that KIC, a mitochondrial fuel, cannot replace glucose in this synergism a nd that mannoheptulose, an inhibitor of glucokinase and glucose-induced ins ulin secretion, abolishes these slow [Ca2+](i) oscillations. In conclusion, these compounds potentiate the effect of glucose. This additive effect is the likely result of a synergistic closing action upon the ATP-sensitive K (K-ATP) channel, mediated in the case of glucose through an action upon th e channel protein itself of ATP generated in glucose catabolism and in the case of tolbutamide. and NBDP upon the sulfonylurea receptor (SUR1) associa ted with this channel. (C) 2001 Elsevier Science Inc. All rights reserved.