Pioglitazone acutely influences glucose-sensitive insulin secretion in normal and diabetic human islets
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 supp...
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| Published in | Biochemical and biophysical research communications Vol. 351; no. 3; pp. 750 - 755 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
22.12.2006
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0006-291X 1090-2104 |
| DOI | 10.1016/j.bbrc.2006.10.103 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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.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. 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. 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. |
| Author | Zhang, Fan Sjöholm, Åke Zhang, Qimin |
| Author_xml | – sequence: 1 givenname: Fan surname: Zhang fullname: Zhang, Fan – sequence: 2 givenname: Åke surname: Sjöholm fullname: Sjöholm, Åke – sequence: 3 givenname: Qimin surname: Zhang fullname: Zhang, Qimin email: Qimin.Zhang@sos.ki.se |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17084385$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:1949905$$DView record from Swedish Publication Index |
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| CitedBy_id | crossref_primary_10_1016_j_metabol_2020_154304 crossref_primary_10_14814_phy2_12014 crossref_primary_10_1152_ajpcell_00444_2008 crossref_primary_10_1016_j_metabol_2021_154821 crossref_primary_10_1007_s00125_021_05505_4 crossref_primary_10_1016_j_lfs_2007_04_034 crossref_primary_10_1111_dom_12935 crossref_primary_10_1152_ajpendo_00388_2009 crossref_primary_10_1210_en_2007_1752 crossref_primary_10_1080_13543784_2025_2463086 |
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| Keywords | Pioglitazone Human islets Glucose sensitivity Diabetes Peroxisome proliferator-activated receptor (PPAR) Cytosolic free Ca 2+ concentration ([Ca 2+] i) Insulin secretion |
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| Snippet | 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,... 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... |
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| SubjectTerms | 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 |
| Title | Pioglitazone acutely influences glucose-sensitive insulin secretion in normal and diabetic human islets |
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