Pancreatic β cells lack a low glucose and O_2-inducible mitochondrial protein that augments cell survival

摘要

β cell failure is a common denominator of diabetes. Susceptibility to stress-induced apoptosis may underlie β cell failure and/or hamper islet transplantation therapy. The causal basis is not well understood. In efforts to identify important differences in gene expression in α vs. β cells, a gene termed HIMP1 (Hypoglycemia/ hypoxia Inducible Mitochondrial Protein, or HIG1) has been cloned from an a cell cDNA library. It is a member of a well conserved eukaryote protein family. In mice, its two alternatively spliced products each form a transmembrane loop, having an N_(outside)-C_(outside) orientation and are expressed highly in the mitochondrial inner membrane in several tissues including heart and pancreatic α cells, but not in β cells. Ectopic expression of HIMP1 in MIN6 β cells protects the cells from apoptosis induced by several stimuli and prolongs their survival. These results suggest an important role for HIMP1 in stress protective programs in mitochondria.