Pioglitazone Reduces Islet Triglyceride Content and Restores Impaired Glucose-Stimulated Insulin Secretion in Heterozygous Peroxisome Proliferator–Activated Receptor-γ–Deficient Mice on a High-Fat Diet
| Autor: | Junji Kamon, Kajuro Komeda, Shunbun Kita, Junji Matsui, Toshimasa Yamauchi, Kazuhiro Eto, Naoto Kubota, Mitsuhiko Noda, Takashi Kadowaki, Tokuyuki Yamashita, Yasuo Terauchi, Iseki Takamoto |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Peroxisome proliferator-activated receptor White adipose tissue Biology Islets of Langerhans Mice chemistry.chemical_compound Insulin resistance Internal medicine Glucose Intolerance Insulin Secretion Internal Medicine medicine Animals Hypoglycemic Agents Insulin Triglycerides DNA Primers Mice Knockout chemistry.chemical_classification Mice Inbred ICR geography geography.geographical_feature_category Base Sequence Pioglitazone Triglyceride medicine.disease Islet Dietary Fats Mice Inbred C57BL PPAR gamma Endocrinology Lipotoxicity chemistry Mice Inbred CBA Thiazolidinediones medicine.drug |
| Zdroj: | Diabetes. 53:2844-2854 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Heterozygous peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-deficient (PPARgamma(+/-)) mice were protected from high-fat diet-induced insulin resistance. To determine the impact of systemic reduction of PPAR-gamma activity on beta-cell function, we investigated insulin secretion in PPARgamma(+/-) mice on a high-fat diet. Glucose-induced insulin secretion in PPARgamma(+/-) mice was impaired in vitro. The tissue triglyceride (TG) content of the white adipose tissue, skeletal muscle, and liver was decreased in PPARgamma(+/-) mice, but it was unexpectedly increased in the islets, and the increased TG content in the islets was associated with decreased glucose oxidation. Administration of a PPAR-gamma agonist, pioglitazone, reduced the islet TG content in PPARgamma(+/-) mice on a high-fat diet and ameliorated the impaired insulin secretion in vitro. Our results demonstrate that PPAR-gamma protects islets from lipotoxicity by regulating TG partitioning among tissues and that a PPAR-gamma agonist can restore impaired insulin secretion under conditions of islet fat accumulation. |
| Databáze: | OpenAIRE |
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