Repaglinide at a cellular level.
To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in rat pancreatic alpha-cells and somatotrophs. We found a pharmacological dissociation between the actions on KATP channels and exocytosis and suggest that compounds that, unlike repaglinide, have direct stimulatory effects on exocytosis in somatotrophs and alpha- and beta-cells, such as sulphonylureas and nateglinide, may have a clinically undesirable general stimulatory effect on cells within the endocrine system.
Krogsgaard Thomsen
M
M
Novo Nordisk, Bagsvaerd, Denmark. mkt@novo.dk
Bokvist
K
K
Høy
M
M
Buschard
K
K
Holst
J J
JJ
Lindström
P
P
Gromada
J
J
D000818:Animals; D002219:Carbamates / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology; D004594:Electrophysiology; D005089:Exocytosis / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D019518:Postprandial Period; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D002219:Carbamates; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D010880:Piperidines; D015221:Potassium Channels; D000077715:Nateglinide; D010649:Phenylalanine; C072379:repaglinide