INSULIN-SECRETION IS REGULATED BY THE GLUCOSE-DEPENDENT PRODUCTION OFISLET BETA-CELL MACROPHAGE-MIGRATION INHIBITORY FACTOR

Macrophage migration inhibitory factor (MIF), originally identified as a cytokine secreted by T lymphocytes, was found recently to be both a pituitary hormone and a mediator released by immune cells in response to glucocorticoid stimulation, We report here that the insulin-secret ing beta cell of the islets of Langerhans expresses MIF and that its p roduction is regulated bg glucose in a time- and concentration-depende nt manner. MIF and insulin colocalize by immunocytochemistry within th e secretory granules of the pancreatic islet beta cells, and once rele ased, MIF appears to regulate insulin release in an autocrine fashion, in perifusion studies performed with isolated rat islets, immunoneutr alization of MIF reduced the first and second phase of the glucose-ind uced insulin secretion response by 39% and 31%, respectively, Converse ly, exogenously added recombinant MIF was found to potentiate insulin release, Constitutive expression of MIF antisense RNA in the insulin-s ecreting INS-1 cell line inhibited MIF protein synthesis and decreased significantly glucose-induced insulin release, MIF is therefore a glu cose-dependent, islet cell product that regulates insulin secretion in a positive manner and may play an important role in carbohydrate meta bolism.