Leptin normalizes the impaired response of proinsulin mRNA to long chain fatty acids in heterozygous zucker diabetic fatty rats

Yan Ting Zhou, Michio Shimabukuro, Young H Lee, Kazunori Koyama, Falguni Trieu, Roger H Unger

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

To determine if underleptinization of islets of Zucker diabetic fatty (ZDF) rats is the proximal cause of their inability to compensate for obesity, we compared the proinsulin/β-actin mRNA ratio in heterozygous (fa/+) ZDF rats with that of wild-type (+/+) and homozygous (fa/fa) ZDF rats. In +/+ islets cultured with 2 mM free fatty acids (FFA) the proinsulin mRNA ratio rose 2.4-fold at 12 h. In fa/+ islets, the ratio rose only 65% above normal. There was no change in fa/fa islets. The presence of leptin (20 ng/ml) in the culture medium increased the FFA-induced response of proinsulin mRNA of fa/+ islets to that of +/+ islets while reducing FFA incorporation into triglycerides. The leptin-induced improvement in the proinsulin mRNA response was independent of any changes in glucose usage. These findings support a causal relationship between diminished leptin action on islets and the impaired β-cell response to FFA in ZDF rats.

Original languageEnglish (US)
Pages (from-to)25648-25651
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number41
DOIs
StatePublished - Oct 10 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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