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- Title
Pioglitazone reduces islet triglyceride content and restores impaired glucose-stimulated insulin secretion in heterozygous peroxisome proliferator-activated receptor-gamma-deficient mice on a high-fat diet.
- Authors
Matsui, Junji; Terauchi, Yasuo; Kubota, Naoto; Takamoto, Iseki; Eto, Kazuhiro; Yamashita, Tokuyuki; Komeda, Kajuro; Yamauchi, Toshimasa; Kamon, Junji; Kita, Shunbun; Noda, Mitsuhiko; Kadowaki, Takashi
- Abstract
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.
- Subjects
INSULIN resistance; DIABETES complications; LIVER cells; ADIPOSE tissues; MICE
- Publication
Diabetes, 2004, Vol 53, Issue 11, p2844
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.11.2844