Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide
Autore:
Sunaga, Y; Gonoi, T; Shibasaki, T; Ichikawa, K; Kusama, H; Yano, H; Seino, S;
Indirizzi:
Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chuo Ku, Chiba 2608670,Japan Chiba Univ Chiba Japan 2608670 r & Mol Med, Chuo Ku, Chiba 2608670,Japan Chiba Univ, Pathogen Fungi & Microbial Toxicoses Res Ctr, Chuo Ku, Chiba 2608673, Japan Chiba Univ Chiba Japan 2608673 es Res Ctr, Chuo Ku, Chiba 2608673, Japan Kissei Pharmaceut Co Ltd, Pharmacol Lab, R&D, Nagano 3998304, Japan KisseiPharmaceut Co Ltd Nagano Japan 3998304 R&D, Nagano 3998304, Japan
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 431, anno: 2001,
pagine: 119 - 125
SICI:
0014-2999(20011109)431:1<119:TEOM(A>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
PANCREATIC BETA-CELLS; POTASSIUM CHANNELS; SKELETAL-MUSCLE; SMOOTH-MUSCLE; RECEPTOR; SUBUNIT; UNRESPONSIVENESS; DESENSITIZATION; GLIBENCLAMIDE; REPERFUSION;
Keywords:
K-ATP channel; sulfonylurea receptor (SUR); mitiglinide; nateglinide; insulin secretion;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Seino, S Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chuo Ku, 1-8-1Inohana,Chiba 2608670, Japan Chiba Univ 1-8-1 Inohana Chiba Japan 2608670hiba 2608670, Japan
Citazione:
Y. Sunaga et al., "The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide", EUR J PHARM, 431(1), 2001, pp. 119-125

Abstract

Mitiglinide (KAD-1229), a new anti-diabetic drug, is thought to stimulate insulin secretion by closing the ATP-sensitive K+ (K-ATP) channels in pancreatic beta -cells. However, its selectivity for the various K-ATP channels is not known. In this study, we examined the effects of mitiglinide on various cloned KATP channels (Kir6.2/SUR1. Kir6.2/SUR2A, and Kir6.2/SUR2B) reconstituted in COS-I cells, and compared them to another meglitinide-related compound, nateglinide. Patch-clamp analysis using inside-out recording configuration showed that mitiglinide inhibits the Kir6.2/SUR1 channel currentsin a dose-dependent manner (IC50 value, 100 nM) but does not significantlyinhibit either Kir6.2/SUR2A or Kir6.2/SUR2B channel currents even at high doses (more than 10 muM). Nateglinide inhibits Kir6.2/SUR1 and Kir6.2/SUR2Bchannels at 100 nM, and inhibits Kir6.2/SUR2A channels at high concentrations (1 muM). Binding experiments on mitiglinide, nateglinide, and repaglinide to SUR1 expressed in COS-1 cells revealed that they inhibit the binding of [H-3]glibenclamide to SUR1 (IC50 values: mitiglinide, 280 nM; nateglinide, 8 muM; repaglinide, 1.6 muM), suggesting that they all share a glibenclamide binding site. The insulin responses to glucose, mitiglinide, tolbutamide, and glibenclamide in MIN6 cells after chronic mitiglinide, nateglinide,or repaglinide treatment were comparable to those after chronic tolbutamide and glibenclamide treatment. These results indicate that, similar to the sulfonylureas, mitiglinide is highly specific to the Kir6.2/SUR1 complex, i.e., the pancreatic beta -cell KATP channel, and suggest that mitiglinide may be a clinically useful anti-diabetic drug. (C) 2001 Published by Elsevier Science B.V.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 10:20:21