Hexosamines and nutrient excess induce leptin production and leptin receptor activation in pancreatic islets and clonal beta-cells

Activation of the hexosamine biosynthesis pathway leads to insulin resistan ce in muscle and adipose tissue. In these tissues leptin gene expression is increased by glucosamine. In the present study we found that glucosamine r apidly activates the production of leptin and OB-Rb, which encodes the func tional leptin receptor, in both primary pancreatic islets and clonal beta - cells. Secretion of leptin from clonal beta -cells into the medium was dete cted readily. In addition, the level of the transcripts encoding signal tra nsducer and activator of transcription-3 and -5, both implicated in leptin signal transduction in islet beta -cells, was increased by glucosamine, alt hough to a lesser degree than mRNA levels of leptin and OB-Rb. High glucose (16.7 mM) induced leptin biosynthesis in primary pancreatic islet cells, a nd the addition of I mm palmitate caused an additional incremental effect. The hexosamine-mediated induction of the leptin system in clonal beta -cell s was associated with increased responsiveness to leptin, as demonstrated b y a 2.6 +/- 0.3-fold (P < 0.01) increase in tyrosine phosphorylation of sig nal transducer and activator of transcription-3. These findings are the fir st evidence of inducible leptin production in pancreatic islets and suggest that islet cells, like skeletal muscle, demonstrate a linkage between incr eased nutrient availability and both leptin expression and leptin responsiv eness.