TNF-alpha inhibits glucose-induced insulin secretion in a pancreatic beta-cell line (INS-1)

Abstract

Recent studies suggest that TNF-alpha affects various biochemical and physiological processes which may be linked to the etiology of non-insulin-dependent diabetes mellitus (NIDDM). For example, TNF-alpha interferes with the signaling of the insulin receptor and the metabolism of glucose transporters. The possibility that TNF-alpha might directly reduce glucose-stimulated insulin secretion in pancreatic beta-cells was examined by using an established pancreatic beta-cell line (INS-1). TNF-alpha did not affect glucose-induced acute insulin secretion (30 min). However, over a longer time period (24 h), TNF-alpha decreased glucose-induced insulin secretion without affecting the total amount of insulin in the cell. In the presence of TNF-alpha levels of 0, 10, 100 and 1000 U/ml, the respective 20 mM glucose-induced insulin secretion was 1.736 +/- 0.166, 1.750 +/- 0.302, 1.550 +/- 0.200, and 1.400 +/- 0.112 mU/ml per 3 x 10(5) cells in 24 h.