Titre du document / Document title

Selectivity of prandial glucose regulators : nateglinide, but not repaglinide, accelerates exocytosis in rat pancreatic A-cells

Auteur(s) / Author(s)

BOKVIST K. ⁽¹⁾ ; HØY M. ⁽¹⁾ ; BUSCHARD K. ⁽²⁾ ; HOLST J. J. ⁽³⁾ ; THOMSEN M. K. ⁽¹⁾ ; GROMADA J. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Novo Nordisk, Novo Alle, 2880 Bagsvaerd, DANEMARK
⁽²⁾ Bartholin Instituttet, Kommunehospitalet, 1399 Copenhagen, DANEMARK
⁽³⁾ Department of Medical Physiology, The Panum Institute, University of Copenhagen, 2200 Copenhagen, DANEMARK

Résumé / Abstract

The effects of the two prandial glucose regulators, repaglinide and nateglinide, on ATP-sensitive K⁺ (K_ATP) channel activity, membrane potential and exocytosis in single rat pancreatic A-cells were investigated using the patch-clamp technique. K_ATP channel activity was reversibly blocked by repaglinide (K_d = 22 nM) and nateglinide (K_d = 410 nM) and this was associated with membrane depolarisation and initiation of electrical activity. The effect of repaglinide and nateglinide on stimulation of glucagon secretion by direct interference with the exocytotic machinery was investigated by the use of capacitance measurements. Nateglinide, but not repaglinide, at concentrations similar to those required to block K_ATP channels potentiated Ca²⁺-evoked exocytosis 3-fold. In αTC1-9 glucagonoma cells addition of nateglinide, but not repaglinide, was associated with stimulation of glucagon secretion. These results indicate that the fast-acting insulin secretagogue nateglinide is glucagonotropic primarily by stimulating Ca²⁺-dependent exocytosis.

Revue / Journal Title

European journal of pharmacology   ISSN 0014-2999   CODEN EJPHAZ 

Source / Source

1999, vol. 386, n^o1, pp. 105-111 (32 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1967) (Revue)

Mots-clés anglais / English Keywords

Nateglinide ; Hypoglycemic agent ; Repaglinide ; Mechanism of action ; Comparative study ; A-Cell ; Pancreas ; Animal ; Rat ; Ionic channel ; Potassium ; In vitro ; Electrophysiology ; Glucagon ; Established cell line ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés français / French Keywords

Natéglinide ; Hypoglycémiant ; Répaglinide ; Mécanisme action ; Etude comparative ; Cellule A ; Pancréas ; Animal ; Rat ; Canal ionique ; Potassium ; In vitro ; Electrophysiologie ; Glucagon ; Lignée cellulaire établie ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés espagnols / Spanish Keywords

Nateglinida ; Hipoglicemiante ; Repaglinida ; Mecanismo acción ; Estudio comparativo ; Célula A ; Páncreas ; Animal ; Rata ; Canal iónico ; Potasio ; In vitro ; Electrofisiología ; Glucagón ; Línea celular establecida ; Rodentia ; Mammalia ; Vertebrata ;

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400008120637.0140