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This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/E510    most recent 00128.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Kawasaki, F. Articles by Kaku, K. Search for Related Content PubMed PubMed Citation Articles by Kawasaki, F. Articles by Kaku, K.

Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice

Diabetes and Endocrine Division, Kawasaki Medical School, Kurashiki-shi, Okayama, Japan

Submitted 17 March 2004 ; accepted in final form 1 November 2004

To evaluate preventive effects of pioglitazone on pancreatic -cell damage in C57BL/KsJ db/db mice, an obese diabetic animal model, the pancreatic islets were compared morphologically between pioglitazone-treated (100 mg/kg daily po) and untreated db/db mice (n = 7 for each) after a 12-wk intervention (6–18 wk of age). The fasting blood glucose level was significantly improved by the treatment with pioglitazone (260 ± 12 vs. 554 ± 62 mg/dl, P < 0.05). The islet mass in the pancreas was significantly greater in pioglitazone-treated mice than in untreated mice (10.2 ± 1.1 vs. 4.6 ± 0.2 mg, P < 0.01). Subsequently, biochemical and physiological analyses of the -cell function were employed using pioglitazone-treated and untreated db/db mice (n = 6 for each) and pioglitazone-treated and untreated db/+ mice (n = 6 for each). After 2 wk of treatment (10–12 wk of age), the plasma levels of triglyceride and free fatty acid were significantly decreased, whereas the plasma adiponectin level increased significantly compared with the untreated group (65.2 ± 18.0 vs. 18.3 ± 1.3 µg/ml, P < 0.05). Pioglitazone significantly reduced the triglyceride content in the islets (43.3 ± 3.6 vs. 65.6 ± 7.6 ng/islet, P < 0.05) with improved glucose-stimulated insulin secretion. Pioglitazone showed no significant effects on the biochemical and physiological parameters in db/+ mice. The present study first demonstrated that pioglitazone prevents -cell damage in an early stage of the disease progression in db/db mice morphologically and physiologically. Our results suggest that pioglitazone improves glucolipotoxicity by increasing insulin sensitivity and reducing fat accumulation in the pancreatic islets.

pancreatic -cells; adiponectin; type 2 diabetes mellitus

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