Pioglitazone acutely influences glucose-sensitive insulin secretion in normal and diabetic human islets |
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Authors: | Zhang Fan Sjöholm Ake Zhang Qimin |
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Institution: | Karolinska Institutet, Department of Internal Medicine, Stockholm South Hospital, SE-11883 Stockholm, Sweden. |
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Abstract: | 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. |
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Keywords: | Pioglitazone Peroxisome proliferator-activated receptor (PPAR) Glucose sensitivity Insulin secretion Cytosolic free Ca2+ concentration ([Ca2+]i) Human islets Diabetes |
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