Pioglitazone acutely influences glucose-sensitive insulin secretion in normal and diabetic human islets

• Published in: Biochemical and biophysical research communications Vol. 351; no. 3; pp. 750 - 755
• Main Authors: Zhang, Fan, Sjöholm, Åke, Zhang, Qimin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.12.2006
• Subjects: Cells, Cultured; Cytosolic free Ca 2+ concentration ([Ca 2+] i); Diabetes; Dose-Response Relationship, Drug; Drug Combinations; Glucose - administration & dosage; Glucose sensitivity; Human islets; Humans; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Kinetics; Middle Aged; Peroxisome proliferator-activated receptor (PPAR); Pioglitazone; Reference Values; Thiazolidinediones - administration & dosage; Time Factors; Pioglitazone; Human islets; Glucose sensitivity; Diabetes; Peroxisome proliferator-activated receptor (PPAR); Cytosolic free Ca 2+ concentration ([Ca 2+] i); Insulin secretion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.10.103

We have studied acute effects of the PPARγ 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.