TNF-alpha inhibits glucose-induced insulin secretion in a pancreatic beta-cell line (INS-1).
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.
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
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D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose