Leptin Normalizes the Impaired Response of Proinsulin mRNA to Long Chain Fatty Acids in Heterozygous Zucker Diabetic Fatty Rats

• Published in: The Journal of biological chemistry 1997-10, Vol.272 (41), p.25648-25651
• Main Authors: Zhou, Yan-Ting, Shimabukuro, Michio, Lee, Young, Koyama, Kazunori, Trieu, Falguni, Unger, Roger H.
• Format: Article
• Language: English
• Subjects: ACIDE GRAS; ACIDOS GRASOS; Actins - genetics; Adipose Tissue - drug effects; Adipose Tissue - metabolism; ANIMAL MODELS; Animals; ARN MENSAJERO; ARN MESSAGER; CARBOHYDRATE METABOLISM; Carrier Proteins - genetics; CONTROL HORMONAL; CONTROLE HORMONAL; DIABETE; DIABETES; Dietary Fats - pharmacology; EXPRESION GENICA; EXPRESSION DES GENES; FATTY ACIDS; Fatty Acids, Nonesterified - pharmacology; GENE EXPRESSION; GENETIC REGULATION; GENETICA; GENETICS; GENETIQUE; GLUCOSA; GLUCOSE; Glucose - pharmacology; HETEROCIGOTOS; HETEROZYGOTE; HETEROZYGOTES; HORMONAL CONTROL; HORMONAS; HORMONE; HORMONES; INSULIN; INSULINA; INSULINE; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Kinetics; Leptin; Male; MESSENGER RNA; METABOLISME DES GLUCIDES; METABOLISMO DE CARBOHIDRATOS; MODELE ANIMAL; MODELOS ANIMALES; Mutagenesis, Site-Directed; Obesity - genetics; PANCREAS; PANCREAS ISLETS; PEPTIDE; PEPTIDES; PEPTIDOS; POLYPEPTIDES; Proinsulin - genetics; Proteins - pharmacology; RAT; RATA; RATS; Rats, Zucker; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.41.25648

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.