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 language | English (US) |
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Pages (from-to) | 25648-25651 |
Number of pages | 4 |
Journal | Journal of Biological Chemistry |
Volume | 272 |
Issue number | 41 |
DOIs | |
State | Published - Oct 10 1997 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology