No abstract

No abstract

No abstract

A bioactive macrophage factor, the polypeptide daintain͞allograft inf lammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the inf luence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain͞AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern -KR-KK-GKR-has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain͞AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain͞AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain͞AIF1 at 75 pmol͞kg inhibited glucose (1 g͞kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol͞kg), daintain͞AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual inf luence on insulin secretion in vivo at different peptide concentrations, and the abundance of macrophages expressing daintain͞AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain͞AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.