Troglitazone ameliorates lipotoxicity in the beta cell line INS-1 expressing PPAR gamma

Toshihide Kawai, Hiroshi Hirose, Yoshiko Seto, Haruhisa Fujita, Hiroshi Fujita, Kaname Ukeda, Takao Saruta

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

To elucidate the mechanisms by which troglitazone, which is a direct ligand for peroxisome proliferator-activated receptor (PPAR) gamma, ameliorates insulin resistance, we have demonstrated that PPAR gamma is expressed in a pancreatic beta cell line, INS-1, using reverse transcription-polymerase chain reaction (RT-PCR). We incubated the cells with 5 μmol/l troglitazone and 1 mmol/l of each major free fatty acid (FFA; palmitic acid, oleic acid, and linoleic acid), alone or in combination, for 48 h. After that, we evaluated glucose-stimulated insulin secretion (GSIS) and 25 mmol/l KCl-induced insulin secretion in the presence of diazoxide, which clamps membrane potential. Our results showed: (1) treatment with troglitazone for 48 h caused enhancement of GSIS, although troglitazone significantly suppressed cell viability assessed by MTT assay. (2) In cells co-treated with troglitazone and FFA, troglitazone ameliorated lipotoxicity due to FFA. (3) In the presence of 300 μmol/l diazoxide and 25 mmol/l KCl, troglitazone did not affect the recovery of GSIS in INS-1 cells. These results suggest that insulin secretion from the rat insulinoma cell line, INS-1, is modulated by troglitazone, acting somewhere in the ATP-sensitive K+ channel pathway, possibly through PPAR gamma.

Original languageEnglish
Pages (from-to)83-92
Number of pages10
JournalDiabetes Research and Clinical Practice
Volume56
Issue number2
DOIs
Publication statusPublished - 2002

Fingerprint

troglitazone
PPAR gamma
Cell Line
Insulin
Diazoxide
Glucose
Insulinoma
Palmitic Acid
Insulin-Secreting Cells
Linoleic Acid
Oleic Acid
Nonesterified Fatty Acids
Membrane Potentials
Reverse Transcription
Insulin Resistance

Keywords

  • ATP-sensitive K channel
  • INS-1 cell
  • Lipotoxicity
  • PPAR gamma
  • Troglitazone

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Troglitazone ameliorates lipotoxicity in the beta cell line INS-1 expressing PPAR gamma. / Kawai, Toshihide; Hirose, Hiroshi; Seto, Yoshiko; Fujita, Haruhisa; Fujita, Hiroshi; Ukeda, Kaname; Saruta, Takao.

In: Diabetes Research and Clinical Practice, Vol. 56, No. 2, 2002, p. 83-92.

Research output: Contribution to journalArticle

Kawai, Toshihide ; Hirose, Hiroshi ; Seto, Yoshiko ; Fujita, Haruhisa ; Fujita, Hiroshi ; Ukeda, Kaname ; Saruta, Takao. / Troglitazone ameliorates lipotoxicity in the beta cell line INS-1 expressing PPAR gamma. In: Diabetes Research and Clinical Practice. 2002 ; Vol. 56, No. 2. pp. 83-92.
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