Pioglitazone acutely influences glucose-sensitive insulin secretion in normal and diabetic human islets.
We have studied acute effects of the PPARgamma agonist pioglitazone in vitro on human islets from both non-diabetic and type 2 diabetic subjects. In 5 mM glucose, pioglitazone caused a transient increase in insulin secretion in non-diabetic, but not diabetic, islets. Continuous presence of the drug suppressed insulin release in both non-diabetic and diabetic islets. In islets from non-diabetic subjects, both high glucose and tolbutamide-stimulated insulin secretion was inhibited by pioglitazone. When islets were continuously perifused with 5 mM glucose, short-term pretreatment with pioglitazone caused approximately 2-fold increase in insulin secretion after drug withdrawal. Pioglitazone pretreatment of diabetic islets restored their glucose sensitivity. Examination of cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in non-diabetic islets revealed slight Ca(2+) transient by pioglitazone at 3 mM glucose with no significant changes at high glucose. Our data suggest that short-term pretreatment with pioglitazone primes both healthy and diabetic human islets for enhanced glucose-sensitive insulin secretion.
Zhang
Fan
F
Karolinska Institutet, Department of Internal Medicine, Stockholm South Hospital, SE-11883 Stockholm, Sweden.
Sjöholm
Ake
A
Zhang
Qimin
Q
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008875:Middle Aged; D000077205:Pioglitazone; D012016:Reference Values; D045162:Thiazolidinediones / Q000008:administration & dosage*; D013997:Time Factors
D004338:Drug Combinations; D007328:Insulin; D045162:Thiazolidinediones; D005947:Glucose; D000077205:Pioglitazone