Pioglitazone hydrochloride stimulates insulin secretion in HIT-T 15 cells by inducing Ca2+ influx.
Pioglitazone hydrochloride (AD-4833), one of the thiazolidinedione analogs, is a new anti-diabetic agent which improves peripheral insulin resistance in diabetic patients. We determined the direct effect of AD-4833 on insulin secretion in HIT-T 15 cells. The effects of AD-4833 (10(-7) M to 10(-5) M) on insulin secretion were examined in 3 and 7 mM glucose-containing F-12 K media. The addition of 10(-5) M AD-4833 significantly increased insulin secretion in both media, but its stimulatory effect was more potent in the medium containing 7 mM glucose. The addition of 10(-5) M AD-4833 caused an immediate, significant increase in cytosolic free Ca2+ concentration ([Ca2+]i). Nifedipine at all concentrations from 10 to 1000 nM significantly attenuated insulin secretion by 10(-5) M AD-4833. In addition, 10(-5) M AD-4833 failed to stimulate insulin secretion in the CA(2+)-free Kreb's-Ringer bicarbonate buffer. These data indicated that AD-4833 stimulates in vitro insulin secretion in HIT-T 15 cells, perhaps by inducing Ca2+ influx.
Ohtani
K
K
First Department of Internal Medicine, Gunma University School of Medicine, Japan.
Shimizu
H
H
Tanaka
Y
Y
Sato
N
N
Mori
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D000077205:Pioglitazone; D013268:Stimulation, Chemical; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D009543:Nifedipine; D005947:Glucose; D002118:Calcium; D000077205:Pioglitazone