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

Diabetes Res Clin Pract. 2002 May;56(2):83-92. doi: 10.1016/s0168-8227(01)00367-9.

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 micromol/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 micromol/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Division / drug effects
  • Cell Survival / drug effects*
  • Chromans / pharmacology*
  • DNA Primers
  • Fatty Acids, Nonesterified / toxicity*
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulinoma
  • Kinetics
  • Linoleic Acid / toxicity
  • Oleic Acid / toxicity
  • Palmitic Acid / toxicity
  • Pancreatic Neoplasms
  • Peroxisomes / drug effects
  • Peroxisomes / physiology
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factors / genetics*
  • Troglitazone
  • Tumor Cells, Cultured

Substances

  • Chromans
  • DNA Primers
  • Fatty Acids, Nonesterified
  • Insulin
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Oleic Acid
  • Palmitic Acid
  • Linoleic Acid
  • Troglitazone