IDENTIFICATION, ISOLATION, AND CHARACTERIZATION OF DAINTAIN (ALLOGRAFT INFLAMMATORY FACTOR-1), A MACROPHAGE POLYPEPTIDE WITH EFFECTS ON INSULIN-SECRETION AND ABUNDANTLY PRESENT IN THE PANCREAS OF PREDIABETIC BB RATS

A bioactive macrophage factor, the polypeptide daintain/allograft infl ammatory 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 influence of the peptide fractions on pancreatic glucose-induced insulin secreti on. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,60 3 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern -KR-KK-GKR- has a motif typical of peptide hormo ne 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 peptid e hormones. Daintain/AIF1 is immunohistochemically localized to microg lial cells in the central nervous system and to dendritic cells and ma crophages in several organs. A particularly dense accumulation of dain tain/AIF1-immunoreactive macrophages was observed in the insulitis aff ecting the pancreatic islets of prediabetic BB rats. When injected int ravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g /kg)-stimulated insulin secretion, with a concomitant impairment of th e glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), d aintain/AIF1 potentiated glucose-stimulated insulin secretion and enha nced the glucose elimination. Its dual influence on insulin secretion in vivo at different peptide concentrations, and the abundance of macr ophages expressing daintain/AIF1 in the pancreatic islets of prediabet ic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.