Objective    To study the influence of leptin on pancreatic β cell insulin synthesis and glucose-stimulated insulin secretion (GSIS) in inflammation.     Methods     INS-1E rat insulinoma cells and freshly isolated rat pancreatic islets cultured in glucose (5.5 mmol/L)-containing media were treated with leptin (0.5 nmol/L or 10 nmol/L)

TNF-α (2 ng/ml or 20 ng/ml)

or their combination (leptin 10 nmol/L and TNF-α 20 ng/ml) for 48 h. Then

the cells and islets were balanced with low-concentration glucose (3.3 mmol/L) for 1 h to test the base level of insulin secretion

and subsequently stimulated with high-concentration glucose (16.7 mmol/L) for 1 h to test GSIS by radioimmunoassay. The expression of proinsulin mRNA was determined by RT-PCR. Intracellular insulin contents were detected after ultrasonic cell disruption.     Results    High-concentration leptin (10 nmol/L) or TNF-α (20 ng/ml) significantly suppressed GSIS (P0.05) and reduced the intracellular proinsulin mRNA level and insulin content (P0.01) in INS-1E cells and pancreatic β cells. However

low-concentration leptin (0.5 nmol/L) or TNF-α (2 ng/ml) did not show such activities. Additionally

when the cultured INS-1E cells or islets were treated with high-concentration leptin (10 nmol/L) plus TNF-α (20 ng/ml)

the intracellular proinsulin mRNA level and insulin content were not further decreased but significantly increased as compared with the results after high-concentration leptin (10 nmol/L) treatment (P0.05)

indicating that TNF-α may antagonize the inhibition effect of leptin on insulin synthesis and secretion.     Conclusion    TNF-α can interfere with leptin-mediated inhibition of insulin synthesis and secretion in pancreatic β cells

and TNF-α level increase may contribute to the genesis of hyperinsulinemia and glucose metabolism disorder in people with obesity.