Troglitazone prevents mitochondrial alterations, β cell destruction, and diabetes in obese prediabetic rats

Moritake Higa, Yan Ting Zhou, Mariella Ravazzola, Danielle Baetens, Lelio Orci, Roger H Unger

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

To determine whether the antidiabetic action of troglitazone (TGZ), heretofore attributed to insulin sensitization, also involves protection of β cells from lipoapoptosis, we treated prediabetic Zucker Diabetic Fatty rats with 200 mg/kg per day of TGZ. Their plasma-free fatty acids and triacylglycerol fell to 1.3 mM and 111 mg/dl, respectively, compared with 2.0 mM and 560 mg/dl in untreated controls. Their islet triacylglycerol content was 34% below controls. In islets of control rats, β cells were reduced by 82% and the islet architecture was disrupted; β-cell glucose transporter-2 was absent, 85% of their mitochondria were altered, and they were unresponsive to glucose. In treated rats, the loss of β cells was prevented, as were the loss of β cell glucose transporter-2, the mitochondrial alterations, and the impairment of glucose-stimulated insulin secretion. We conclude that the antidiabetic effect of TGZ in prediabetic Zucker Diabetic Fatty rats involves prevention of lipotoxicity and lipoapoptosis of β cells, as well as improvement in insulin sensitivity.

Original languageEnglish (US)
Pages (from-to)11513-11518
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number20
DOIs
StatePublished - Sep 28 1999

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troglitazone
Facilitative Glucose Transport Proteins
Hypoglycemic Agents
Triglycerides
Insulin
Glucose
Cytoprotection
Nonesterified Fatty Acids
Insulin Resistance
Mitochondria

Keywords

  • Lipoapoptosis
  • Lipotoxicity
  • Zucker Diabetic Fatty rats

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Troglitazone prevents mitochondrial alterations, β cell destruction, and diabetes in obese prediabetic rats. / Higa, Moritake; Zhou, Yan Ting; Ravazzola, Mariella; Baetens, Danielle; Orci, Lelio; Unger, Roger H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 20, 28.09.1999, p. 11513-11518.

Research output: Contribution to journalArticle

Higa, Moritake ; Zhou, Yan Ting ; Ravazzola, Mariella ; Baetens, Danielle ; Orci, Lelio ; Unger, Roger H. / Troglitazone prevents mitochondrial alterations, β cell destruction, and diabetes in obese prediabetic rats. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 20. pp. 11513-11518.
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