Pancreatic beta cells lack a low glucose and O2-inducible mitochondrial protein that augments cell survival

Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10636-41. doi: 10.1073/pnas.0604194103. Epub 2006 Jun 30.

Abstract

beta cell failure is a common denominator of diabetes. Susceptibility to stress-induced apoptosis may underlie beta 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 alpha vs. beta cells, a gene termed HIMP1 (Hypoglycemia/hypoxia Inducible Mitochondrial Protein, or HIG1) has been cloned from an alpha 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 alpha cells, but not in beta cells. Ectopic expression of HIMP1 in MIN6 beta 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Glucose / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • Intracellular Membranes / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / physiology*
  • Molecular Sequence Data
  • Oxygen / physiology*

Substances

  • Hig1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Glucose
  • Oxygen

Associated data

  • GENBANK/AY028386
  • GENBANK/AY028387